The cellular basis of tumor progression

International Review of Cytology

Volumn 177, Issue , 1997, Pages 1-56

  Heppner, Gloria H ^a   Miller, Fred R ^a  

^a KARMANOS CANCER INSTITUTE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

REACTIVE OXYGEN METABOLITE;

ANIMAL EXPERIMENT; ANIMAL MODEL; CANCER CELL; CANCER GROWTH; CANCER RESEARCH; CANCER THERAPY; CELL DIFFERENTIATION; CELL FUSION; CELL INFILTRATION; CELL INTERACTION; CELL SUBPOPULATION; CHROMOSOME ABERRATION; CYTOLOGY; DNA DAMAGE; DNA METHYLATION; DNA REPAIR; GENE AMPLIFICATION; GENE EXPRESSION REGULATION; GENE MUTATION; GENETIC STABILITY; GENETIC VARIABILITY; HUMAN; INFLAMMATORY CELL; METASTASIS; MUTATION RATE; NONHUMAN; PRIORITY JOURNAL; PROGNOSIS; REVIEW; TUMOR GROWTH;

ANIMALIA;

EID: 0030830309     PISSN: 00747696     EISSN: None     Source Type: Book Series    
DOI: 10.1016/s0074-7696(08)62230-5     Document Type: Article

References (319)

1. Aabo, K., Roed, H., Vindelov, L. L., and Spang-Thomson, M. (1994). A dominated and resistant subpopulation causes regrowth after response to 1,3-Bis (2-chloroethyl 1)-1nitrosourea treatment of a heterogeneous small cell lung cancer xenograft in nude mice. Cancer Res. 54, 3295-3299.
2. Aabo, K., Vindelov, L. L., and Spang-Thomson, M. (1995). Clonal dominance between subpopulations of mixed small cell lung cancer xenografts implanted ectopically in nude mice. Eur. J. Cancer 31A, 222-229.
3. Abbruzzese, J. L., Abbruzzese, M. C, Hess, K. R., Raber, M. N., Lenzi, R., and Frist, P. (1994). Unknown primary carcinoma: Natural history and prognostic factors in 657 consecutive patients. J. Clin. Oncol: 12, 1272-1280.
4. Alam, S. M., Whitford, P., Cushley, W., George, W. D., and Campbell, A. M. (1992). Aneuploid subpopulations in tumor invaded lymph nodes from breast cancer patients. Eur. J. Cancer 28, 357-362.
5. Albino, A. P., Lloyd, K. O., Houghton, A. N., Oettgen, H. F., and Old, L. J. (1981). Heterogeneity in surface antigen and glycoprotein expression of all cell lines derived from different melanoma metastases of the same patient. J. Exp. Med. 154, 1764-1778.
6. Alers, J. C., Krijtenburg, P. J., Vissers, C. J., Bosman, F. T., van der Kusast, T. H., and van Dekken, H. (1995). Cytogenetic heterogeneity and histologie tumor growth patterns in prostatic cancer. Cytometry 21, 84-94.
7. Allalunis-Turner, M. J., Barron, G. M., Day, R. S., Dobler, K., and Urtasun, R. C. (1992). Heterogeneity in response to treatment with buthionine sulfoximine or interferon in human malignant glioma cells. Int. J. Radiat. Oncol. Diol. Pliys. 22, 765-768.
8. Alvarez, E., Elliott, B. E., Houghton, A. N., and Kerbel, R. S. (1988). Heritable high frequencymodulation of antigen expression in neoplastic cells exposed to 5-aza-2′-deoxycytidine or hydroxyurea: Analysis and implications. Cancer Res. 48, 2440-2445.
9. Azizi, E., Fiedman, J., Pavlotsky, F., Iscovich, J., Bornstein, A., Shafir, R., Trau, H., Brenner, H., and Nass, D. (1995). Familial cutaneous malignant melanoma and tumors of the nervous system-a hereditary cancer syndrome. Cancer 76, 1571-1578.
10. Balazs, M., Matsumura, K., Moore, D., Pinkel, D., Grey, J. W., and Waldman, F. M. (1995). Karyotypic heterogeneity and its relation to labeling index in interphase breast tumor cells. Cytometry 20, 62-73.
11. Baroffio, A., Bouhaton-Prallat, M.-L., Gabbiani, G., and Bader, C. R. (1995). Heterogeneity in the progeny of single human muscle satellite cells. Differentation 59, 259-268.
12. Beerman, H., Smit, V. T. H. B. M., Kluin, P. M., Bonsing, B. A., Hermans, J., and Cornelisse, C. J. (1991). Flow cytometric analysis of DNA stemline heterogeneity in primary and metastatic breast cancer. Cytometry 12, 147-154.
13. Bennett, D. C, Peachey, L. A., Durbin, H., and Rudland, P. S. (1978). A possible mammary stem cell line. Cell 15, 283-298.
14. Bichel, P. (1972). Specific growth regulation in three ascitic tumors. Eur. J. Cancer 8, 167-173.
15. Bieche, F., deMurcia, G., and Lidereau, R. (1996). Poly (ADP-ribose) polymerase gene expression status and genomic instability in human breast cancer. Clin. Cancer Res. 2, 1163-1167.
16. Biswas, C, Moran, W. P., Bloch, K. J., and Gross, J. (1978). Collagenolytic activity of rabbit V2-carcinoma growing at multiple sites. Biochem. Biophys. Res. Commun. 80, 33-38.
17. Boone, C. W., Vembu, D., White, B. J., Takeichi, N., and Parajpe, M. (1979). Karyotypic, antigenic, and kidney-invasive properties of cell lines form fibrosarcomas arising in C3H/10T1/2 cells implanted subcutaneously attached to plastic plates. Cancer Res. 39, 2172-2178.
18. Brattain, M. G., Fine, W. D., Khalel, F. M., Thompson, J., and Brattain, D. E. (1981). Heterogeneity of malignant cells from human colonie carcinomas. Cancer Res. 41, 1751-1756.
19. Brattain, M. G., Marks, M. E., McCombs, J., Finley, W., and Brattain, D. E. (1983). Characterization of human colon carcinoma cell lines isolated from a single primary tumour. Br. J. Cancer 47, 373-381.
20. Brennan, M. J., Donigan, W. L., and Appleby, D. E. (1979). The variability of estrogen receptors in metastatic breast cancer. Am. J. Surg. 137, 260-262.
21. Brentnall, T. A., Crispin, D. A., Bronner, M. P., Cherian, S. P., Hueffed, M., Rabinovitch, P. S., Rubin, C. E., Haggitt, R. C, and Boland, C. R. (1996). Microsatellite instability in nonneoplastic mucosa from patients with chronic ulcerative colitis. Cancer Res. 56, 1237-1240.
22. Britten, R. A., Evans, A. J., Allalunis-Turner, M. J., Franko, A. J., and Pearcey, R. G. (1996). Intratumoral heterogeneity as a confounding factor in clonogenic assays for tumor radioresponsiveness. Radiother. Oncol. 39, 145-153.
23. Brodt, P., Parker, R., Sarkar, P., and LaLa, P. K. (1985). Studies on clonal heterogeneity in two spontaneously metastasizing mammary carcinomas of recent origin. Int. J. Cancer 35, 265-273.
24. Brown, J. L., Russell, P. J., Phillips, J., Wotherspoon, J., and Raghaven, D. (1990). Clonal analyses of a bladder cancer cell line: An experimental model of tumour heterogeneity. Br. J. Cancer 61, 369-376.
25. Browning, H. C. (1948). Heterologous and homologous growth of transplants during the course of development of spontaneous mammary tumors in C3H mice. JNCI, J. Natl. Cancer Inst. 8, 173-189.
26. Caignard, A., Martin, M. S., Michel, M. F., and Martin, F. (1985). Interaction between two cellular populations of a rat colonie carcinoma when inoculated to the syngeneic host. Int. J. Cancer 36, 273-279.
27. Califano, J., van der Riet, P., Westra, W., Nawroz, H., dayman, G., Piantadosi, S., Corio, R., Lee, D., Greenberg, B., Koch, W., and Sidransky, D. (1996). Genetic progression model for head and neck cancer: implications for field cancerization. Cancer Res. 56, 2488-2492.
28. Ceriani, R. L., Peterson, J. A., and Blank, E. W. (1984). Variability in surface antigen expression of human breast epithelial cells cultured from normal breast, normal tissue peripheral to breast carcinomas and breast carcinomas. Cancer Res. 44, 3033-3039.
29. Chambers, A. F., Hill, R. P., and Ling, V. (1981). Tumor heterogeneity and stability of the metastatic phenotype of mouse KHT sarcoma cells. Cancer Res. 41, 1368-1372.
30. Cheshire, P. J. (1970). The effect of multiple tumours on mammary tumour growth rates in the C3H mouse. Br. J. Cancer 24, 542-547.
31. Chong, Y. C, Heppner, G. H., Paul, L. A., and Fulton, A. M. (1989). Macrophagc-mediated induction of DNA strand breaks in target tumor cells. Cancer Res. 46, 6652-6657.
32. Cifone, M. A., and Fidler, I. J. (1981). Increasing metastatic potential is associated with increasing genetic instability of clones isolated from murine neoplasms. Proc. Natl. Acad. Sei. USA 78, 6249-6252.
33. Cillo, C, Dick, J. E., Ling, V., and Hill, R. P. (1987). Generation of drug-resistant variants in metastatic B16 mouse melanoma cell lines. Cancer Res. 47, 2604-2608.
34. Coons, S. W., Johnson, P. C, and Shapiro, J. R. (1995). Cytogenetic and flow cytometry DNA analysis of regional heterogeneity in a low grade human glioma. Cancer Res. 55,1569-1577.
35. Culver, K. W., Ram, Z., Wallbridge, S., Ishii, H., Oldfield, E. H., and Blaese, R. M. (1992). In vivo gene transfer with retroviral-producer cells for treatment of experimental brain tumors. Science 256, 1550-1552.
36. Czarnecki, D., Tait, B., Nicholson, I., and Lewis, A. (1994). Multiple non-melanoma skin cancer: evidence that different MHC genes are associated with different cancers. Dermatol-ogy 188, 88-90.
37. Daley, M. J. (1981). Intratumor maturational heterogeneity with the murine myeloma MOPC-315. Cancer Res. 41, 187-191.
38. Damen, J. E., Tagger, A. Y., Greenberg, A. H., and Wright, J. A. (1989). Generation of metastatic variants in populations of mutator and amplificator mutants. JNCI, J. Natl. Cancer Inst. 81, 628-631.
39. Danielpour, D., and Sirbasku, D. A. (1984). New perspectives in hormone-dependent (responsive) and autonomous mammary tumor growth: role of autostimulatory growth factor. In Vitro 20, 975-980.
40. Dawson, P. J., Wolman, S. R., Tait, L., Heppner, G. H., and Miller, F. R. (1996). MCF10AT: A model for the evolution of cancer from proliferative breast disease. Am. J. Pathol. 148, 313-319.
41. DeBaetselier, P., Gorelik, E., Eshhar, Z., Ron, Y., Katzav, S., Feldman, M., and Segal, S. (1981). Metastatic properties conferred on non-metastatic tumours by hybridization of spleen B-lymphocytes with plasmacytoma cells. JNCI, J. Natl. Cancer Inst. 67, 1079-1087.
42. de Vries, E. G. E., Meijer, C, Timmer-Bosscha, H., Berendsen, H. H., de Leij, L., Schaper, R. J., and Mulder, N. H. (1989). Resistance mechanisms in three human small cell lung cancer cell lines established from one patient during clinical follow-up. Cancer Res. 49, 4175-4178.
43. Dexter, D. L., Kowalski, H. M., Blazar, B. A., Fligiel, Z., Vogel, R., and Heppner, G. H. (1978). Heterogeneity of tumor cells from a single mouse mammary tumor. Cancer Res. 38, 3174-3181.
44. Diala, E. S., Cheah, M. S. C, Rowitch, D., and Huffman, R. M. (1983). Extent of DNA methylation in human tumor cells. JNCI, J. Natl. Cancer Inst. 71, 755-764.
45. Dizdaroglu, M., Olinski, R., Doroshow, J. H., and Akman, S. A. (1993). Modification of DNA bases in chromatin of intact target human cells by activated human polymorphonuclear leucocytes. Cancer Res. 53, 1269-1272.
46. Dominguez, O. V., and Huseby, R. A. (1968). Heterogeneity of induced testicular interstitial cell tumors of mice as evidenced by steroid biosynthetic enzyme activities. Cancer Res. 28, 348-353.
47. Duggan, B. D., Felix, J. C, Muderspach, L. I., Tourgeman, D., Zheng, J., and Shibuta, D. (1994). Microsatellite instability in sporadic endometrial carcinoma. J. Natl. Cancer Inst. 86, 1216-1221.
48. Dulbecco, R., and Armstrong, B. (1988). Stochastic development of invasive potential in rat mammary tumors induced by N-methyl-N-nitrosourea. Proc. Natl. Acad. Sci. USA 85, 8659-8663.
49. Dulbecco, R., Armstrong, B., Allen, W. R., and Bowman, M. (1986). Distribution of developmental markers in rat mammary tumors induced by N-nitrosourea. Cancer Res. 46, 5142-5144.
50. Edwards, R. E., Hill, R. J., Brown, D. G., and Carthew, P. (1990). Phenotypic stability and metastatic behavior of serially xenografted rat mesothaliomas. Dr. J. Cancer 62, 201-208.
51. Eldridge, S. R., and Gould, M. N. (1992). Comparison of spontaneous mutagenesis in early passage human mammary cells from normal and malignant tissue. Int. J. Cancer 50, 321-324.
52. Eng, C., Mulligan, L. M., Healey, C. S., Houghton, C, Frilling, A., Rave, F., Thomas, G. A., and Ponder, B. A. J. (1996). Heterogeneous mutation of the RET proto-oncogene in subpopulations of medullary thyroid carcinoma. Cancer Res. 56, 2167-2170.
53. Fante, R., Roncucci, L., Di Gregorio, C, Tamassia, M. G., Losi, L., Benatti, P., Pedroni, M., Percesepe, A., De Pietri, S., and Ponz de Leon, M. (1996). Frequency and clinical features of multiple tumors of the large bowel in the general population and in patients with hereditary colorectal carcinoma. Cancer 77, 2013-2021.
54. Farber, E., and Rubin, H. (1991). Cellular adapatations in the origin and development of cancer. Cancer Res. 51, 2751-2761.
55. Fargion, S., Carney, D., Mulshine, J., Rosen, S., Bunn, P., Jewett, P., Cuttitta, F., Gazdar, A., and Minna, J. (1986). Heterogeneity of cell surface antigen expression of human small cell lung cancer detected by monoclonal antibodies. Cancer Res. 46, 2633-2638.
56. Fearon, E. R., and Vogelstein, B. A. (1990). A genetic model for colorectal tumorigeneis. Cell 61, 759-767.
57. Feig, D. I., Reid, T. M., and Loeb, L. A. (1994). Reactive oxygen species in tumorigenesis. Cancer Res. 54, 1890s-1894s.
58. Feinberg, A., and Vogelstein, B. (1983a). Hypomethylation distinguishes genes of some human cancers from their normal counterparts. Nature (London) 301, 89-92.
59. Feinberg, A. P., and Vogelstein, B. (1983b). Hypomethylation of ras oncogenes in primary human cancers. Biochem. Biophys. Res. Commun. 111, 47-54.
60. Ferguson, P. J., and Cheng, Y. (1989). Phenotypic instability of drug sensitivity in a human colon carcinoma cell line. Cancer Res. 49, 1148-1153.
61. Fialkow, P. J. (1979). Clonal origin of human tumors. Annu, Rev. Med. 30, 135-143.
62. Fidler, I. J., and Kripke, M. L. (1977). Metastasis results from pre-existing variant cells within a malignant tumor. Science 197, 893-895.
63. Fiegl, M., Tueni, C., Schenk, T., Jakesz, R., Gnant, M., Reiner, A., Rudes, M., Pirc-Danoewinata, H., Marosi, C., Huber, H., and Drach, J. (1995). Interphase cytogenetics reveals a high incidence of aneuploidy and intra-tumour heterogeneity in breast cancer. Br. J. Cancer 72, 51-55.
64. Fishel, R. (1996). Genomic instability, mutators, and the development of cancer: Is there a role for p53? J. Natl Cancer lust. 88, 1608-1609.
65. Fishel, R., Lescoe, M. K., Rao, M. R. S., Copeland, N. G., Jenkins, N. A., Garber, J., Kane, M., and Kolodner, R. (1993). The human mutator gene homolog MSH2 and its association with hereditary nonpolyposis colon cancer. Cell 75, 1027-1038.
66. Fisher, B., Gunduz, N., Coyle, J., Rudock, C, and Saffer, E. (1989). Presence of a growth-stimulating factor in serum following primary tumor removal in mice. Cancer Res. 49,1996-2001.
67. Flatau, E., Bogenmann, E., and Jones, P. A. (1983). Variable 5-methylcytosine levels in human tumor cell lines and fresh pediatric tumor expiants. Cancer Res. 43, 4901-4905.
68. Foulds, L. (1969). "Neoplastic Development," Vol. 1. Academic Press, New York.
69. Foulds, L. (1975). "Neoplastic Development," Vol. 1. Academic Press, New York.
70. Frankfurt, O. S., Seckinger, D., and Sugarbaker, E. V. (1991). Intercellular transfer of drug resistance. Cancer Res. 51, 1190-1195.
71. Freeman, S. M., Abboud, C. N., Whartenby, K. A., Packman, C. H., Koeplin, D. S., Moolten, F. L., and Abraham, G. N. (1993). The "bystander effect": Tumor regression when a fraction of the tumor mass is genetically modified. Cancer Res. 53, 5274-5283.
72. Frost, P., Liteplo, R. G., Donaghue, T. P., and Kerbel, R. S. (1984). Selection of strongly immunogenic "TUM-" variants from tumors at high frequency using 5-azacytidine. J. Exp. Med. 149, 1491-1501.
73. Frost, P., Kerbel, R. S., Hunt, B., Man, S., and Pathak, S. (1987). Selection of metastatic variants with identifiable karyotypic changes from a nonmctastatic murine tumor after treatment with 2'-deoxy-5-azacytidine or hydroxyurea: Implications for mechanisms of tumor progression. Cancer Res. 47, 2690-2695.
74. Fucci, L., Pirrelli, M., and Caruso, M. L. (1994). Carcinoma and synchronous hyperplastic polyps of the large bowel. Pathologica 86, 371-375.
75. Fuhr, J. E., Frye, A., Kattine, A. A., and Van Meter, S. (1991). Flow cytometric determination of breast tumor heterogeneity. Cancer 67, 1401-1405.
76. Fujii, H., Marsh, C., Carnes, P., Sidransky, D., and Gabrielson, E. (1996). Genetic divergence in the clonal evolution of breast cancer. Cancer Res. 56, 1493-1497.
77. Fujimaki, E., Sasaki, K., Nakano, O., Chiba, S., Tazawa, H., Yamashiki, H., Orii, S., and Sugai, T. (1996). DN A ploidy heterogeneity in early and advanced gastric cancers. Cytometry 26, 131-136.
78. Fulton, A. M., Loveless, S. E., and Heppner, G. H. (1984). Mutagenic activity of tumorassociated macrophages in Salmonella typhimurium strains TA98 and TA100. Cancer Res. 44, 4308-4311.
79. Gagos, S., Iliopoulos, D., Tscleni-Balafouta, S., Agapitos, M., Antachupoulos, C., Kostakis, A., Karayannakos, P., and Skalkeas, G. (1996). Cell senescence and a mechanism of clonal evolution leading to continuous cell proliferation, loss of heterozygosity, and tumor heterogeneity: Studies on two immortal colon cancer cell lines. Cancer Genet. Cytogenet. 90, 157-165.
80. Geradts, J., Richards, J., Edery, M., Pang, K., Larson, L., and Nandi, S. (1986). Heterogeneity in the hormonal responsiveness of clones derived from the 13762 NF rat mammary tumor. Cancer Res. 46, 1920-1927.
81. Gerharz, C. D., Gabbert, H. E., Engers, R., Ramp, U., Mayer, H., Bicsalski, H. K., and Luley, G. (1989). Heterogeneous response to differentiation induction in different clonal subpopulations of a rat rhabdomyosarcoma cell line (BA-HAN-1). Cancer Res. 49, 7132-7140.
82. Giaretti, W., Monaco, R., Pujic, N., Rapallo, A., Nigro, S., and Geido, E. (1996). Intratumor heterogeneity of K-ras a mutations in colorectal adenocarcinomas. Am. J. Pathol. 149, 237-245.
83. Giavazzi, R., Alessandri, G., Spreafico, F., Garattini, S., and Mantovani, A. (1980). Metastasizing capacity of tumour cells from spontaneous metastases of transplanted murine tumours. Br. J. Cancer 42, 462-472.
84. Gitelman, I., Dexter, D. F., and Roder, J. C. (1987). DNA amplification and metastases of the human melanoma cell line MeWo. Cancer Res. 47, 3851-3855.
85. Glick, A. B., Weinberg, W. C, Wu, I. H., Quan, W., and Yuspa, S. A. (1996). Transforming growth factor Bl suppresses genomic instability independent of a Gl arrest, p53 and Rb. Cancer Res. 56, 3645-3650.
86. Goelz, S. E., Vogelstein, B., Hamilton, S. R., and Feinberg, A. P. (1985). Hypomethylation of DNA from benign and malignant human colon neoplasms. Science 228, 187-198.
87. Goldenberg, D. M., Pavia, R. A., and Tsao, M. C. (1974). In vivo hybridization of human tumour and normal hamster cells. Nature (London) 250, 649-651.
88. Goldie, J. H., and Coldman, A. J. (1984). The genetic origin of drug resistance in neoplasms: implications for systemic therapy. Cancer Res. 44, 3643-3653.
89. Good, D. J., Polverini, P., Rastinejad, F., LeBeau, M. M., Lemons, R. S., Frazier, W. A., and Bouck, N. P. (1990). A tumor suppressor-dependent inhibitor of angiogenesis is immunologically and functionally indistinguishable from a fragment of thrombospondin. Proc. Natl. Acad. Sci. USA 87, 6624-6628.
90. Gorelik, E., Segal, S., and Feldman, M. (1978). Growth of a local tumor exerts a specific inhibitory effect on progression of lung metastases. Int. J. Cancer 21, 617-625.
91. Gorelik, E., Segal, S., and Feldman, M. (1981). On the mechanism of tumor "concomitant" immunity. Int. J. Cancer 27, 847-856.
92. Greenblat, M. S., Bennett, W. P., Hollstein, M., and Harris, C. C. (1994). Mutations in the p53 tumor suppressor gene: Clues to cancer etiology and molecular pathogenesis. Cancer Res. 54, 4855-4878.
93. Griffen, J. E., Allman, D. R., Durrant, J. L., and Wilson, J. D. (1980). Variation in steroid 5a-reductase activity in cloned human skin fibroblasts. J. Biol. Chem. 256, 3662-3666.
94. Grundel, R., and Rubin, H. (1991). Effect of interclonal heterogeneity on the progressive, confluence-mediated acquisition of the focus-forming phenotype in NIH-3T3 populations. Cancer Res. 51, 1003-1013.
95. Hager, J. C., Miller, F. R., and Heppner, G. H. (1978). Influence of serial transplantation on the immunological-clinical correlates of BALB/cfC3H mouse mammary tumors. Cancer Res. 38, 2492-2500.
96. Hager, J. C., Fligiel, S., Stanley, W., Richardson, A. M., and Heppner, G. H. (1981). Characterization of a variant-producing tumor cell line from a heterogeneous strain Balb/cfC3H mouse mammary tumor. Cancer Res. 41, 1293-1300.
97. Hakansson, L., and Trope, C. (1974b). Cell clones with different sensitivity to cytostatic drugs in methylcholanthrene-induced mouse sarcomas. Ada Pathol. Microbiol. Scand. Secti A 82, 41-47.
98. Hakansson, L., and Trope, C. (1974a). On the presence within tumours of clones that differ in sensitivity to cytostatic drugs. Acta Pathol. Microbiol. Scand., Sect A 82A, 35-40.
99. Han, H.-J., Yanagisawa, A., Kato, Y., Park, J.-G., and Nakamura, Y. (1993). Genetic instability in pancreatic cancer and poorly differentiated type of gastric cancer. Cancer Res. 53, 5087-5099.
100. Hand, P. H., Nuti, M., Colcher, D., and Schlom, J. (1983). Definition of antigenic heterogeneity and modulation among human mammary carcinoma cell populations using monoclonal antibodies to tumor-associated antigens. Cancer Res. 43, 728-735.
101. Harris, J. F., Chambers, A. F., Hill, R. P., and Ling, V. (1982). Metastatic variants are generated spontaneously at a high rate in mouse KHT tumor. Proc. Natl. Acad. Sci. USA 79, 5547-5551.
102. Hart, I. R. (1984). Tumor cell hybridization and neoplastic progression. In "Cancer Invasion and Metastasis: Biological and Therapeutic Aspects" pp. 133-143. Raven Press, New York.
103. Hauschka, T. S. (1953). Methods of conditioning the graft in tumor transplantation. JNCI, J. Natl. Cancer Inst. 14, 723-736.
104. Hennessey, T. L., and Rubin, H. (1986). Development and inheritance of osmotic tolerance in a line of spontaneously transformed Balb/c/3T3 cells. Cancer Res. 46, 6041-6048.
105. Heppner, G. H. (1989). Tumor cell societies. JNCI, J. Natl. Cancer Inst. 81, 648-649.
106. Heppner, G. H., and Miller, B. E. (1989). Therapeutic implications of tumor heterogeneity. Semin. Oncol. 16, 91-105.
107. Heppner, G. H., Dexter, D. R., DeNucci, T., Miller, F. R., and Calabresi, P. (1978). Heterogeneity in drug'sensitivity among tumor cell subpopulations of a single mouse mammary tumor. Cancer Res. 38, 3758-3763.
108. Heppner, G. H., Miller, B., Cooper, D. N., and Miller, F. R. (1980). Growth interactions between mammary tumor cells. In "Cell Biology of Breast Cancer" (C.M. McGrath, M.J. Brennan, and M.A. Rich, eds.), pp. 161-172. Academic Press, New York.
109. Hill, H. Z., Hill, G. J., Miller, C. F., Kwong, F., and Purdy, J. (1979). Radiation and melanoma response of B16 mouse tumor cells and clonal lines to in vitro irradiation. Radiat. Res. 80, 259-276.
110. Hill, R. P., Chambers, A. F., Ling, V., and Harris, J. F. (1984). Dynamic heterogeneity: Rapid generation of metastatic variants in mouse B16 melanoma cells. Science 224, 998-1001.
111. Huffman, R. M. (1984). Altered methionine metabolism, DNA methylation and oncogene expression. Biochim. Biophys. Acta 738, 49-87.
112. Holliday, R. (1987). The inheritance of epigenetic defects. Science 238, 163-170.
113. Horvath, G., Ferno, M., Baldetori, B., and Johansson, M. (1993). Growth interaction between different tumor populations in human endometrial adenocarcinoma growing in nude mice. In Vivo 7, 511-518.
114. Hosteller, L. W., and Kripke, M. L. (1988). Proportion of antigenic variants induced by in vitro uv irradiation differs in clones derived from a single tumor. J. Immunol. 140, 666-670.
115. Hsu, S. H., Luk, G., Krush, A. J., Hamilton, S. R., and Hoover, H. H. (1983). Multiclonal origin of polyps in Gardner Syndrome. Science 221, 951-953.
116. Hughes, N. R., Walls, R. S., Newland, R. C., and Payne, J. E. (1986). Gland to gland heterogeneity in histologically normal mucosa of colon cancer patients demonstrated by monoclonal antibodies to tissue-specific antigens. Cancer Res. 46, 5993-5999.
117. Ichikawa, T., Akimoto, S., Hayata, S., and Shimazaki, J. (1989). Progression and selection in heterogeneous tumor composed of androgen-responsive Shionogi Carcinoma 115 and its autonomous subline (Chiba subline 2). Cancer Res. 49, 367-371.
118. Imada, M., and Sueoka, N. (1978). Clonal sublines of rat neurotumor RT4 and cell differentiation. Dev. Biol. 66, 97-108.
119. Isaacs, J. T., Wake, N., Coffey, D. S., and Sandberg, A. A. (1982). Genetic instability coupled to clonal selection as a mechanism for tumor progression in the Dunning R-3327 rat prostatic adenocarcinoma system. Cancer Res. 42, 2353-2361.
120. Itaya, T., Judde, J.-G., Hunt, B., and Frost, P. (1989). Genotypic and phenotypic evidence of clonal interactions in murine tumor cells. JNCI, J. Natl. Cancer Inst. 81, 664-668.
121. Jacob, R., Welkoborsky, H. J., Mann, W. J., Hofken, F., Dienes, H. P., and Frieje, J. E. (1996). Heterogeneity of squamous cell carcinomas of the head and neck-Analysis of tumor biologic factors and proliferation rates. Laryngoscope 106, 1170-1175.
122. Jakubezak, J. L., Merlino, G., French, J. E., Muller, W. J., Paul, B., Adhya, S., and Garges, S. (1996). Analysis of genetic instability during mammary tumor progression using a novel selection-based assay for in vivo mutations in a bacteriophage transgene target. Proc. Natl. Acad. Sci. USA 93, 9073-9078.
123. Jamasbi, R. J., and Perkins, E. H. (1990). Biological heterogeneity and radiation sensitivity of in vitro propagated lung metastatic lines originated from a transplantable squamous cell carcinoma of BALB/c mouse. In Vitro Cell Dev. Biol. 26, 222-228.
124. Jenner, K., Darnton, S. J., Billingham, L., Warfield, A. T., and Matthews, H. R. (1996). Tumour heterogeneity: A problem in biopsy assessment of the proliferation index of oesophageal adenocarcinomas. /. Clin. Pailiol. Mol. Pathol. 49, M61-M63.
125. Jones, P. A. (1996). DNA methylation errors and cancers. Cancer Res. 56, 2463-2467.
126. Jouanneau, J., Moens, G., Bourgeois, Y., Poupon, M. F., and Thierry, J. P. (1994). A minority of carcinoma cells producing acidic fibroblast growth factor induces a community effect for tumor progression. Proc. Nail. Acad. Sci. USA 91, 286-290.
127. Kadcn, D., Gadi, I. K., Bardwell, L., Gelman, R., and Sager, R. (1989). Spontaneous mutation rates of tumorigenic and nontumorigenic Chinese hamster embryo fibroblast cell lines. Cancer Res. 49, 3374-3379.
128. Kahlenberg, M. S., Stoler, D. L., Basik, M., Petrelli, N. J., Rodriquez-Bigas, M., and Anderson, G. (1996). p53 tumor suppressor gene status and the degree of genomic instability in sporadic colorectal cancer. JNCI, J. Natl. Cancer Insl. 88, 1665-1670.
129. Kasid, A., Knabbe, G., and Lippman, M. E. (1987). Effect of v-rasH oncogene transfection on estrogen-independent tumorigenicity of estrogen-dependent human breast cancer cells. Cancer Res. 47, 5733-5738.
130. Katsura, K., Sugihara, H., Nakai, S., and Fujita, S. (1996). Alteration of numerical chromosomal aberrations during progression of colorectal tumors revealed by a combined fluorescence in situ hybidization and DNA ploidy analysis of intratumoral heterogeneity. Cancer Genet. Cytogenet. 90, 146-153.
131. Keller, R. (1985). Repression of lymphatic metastasis by a second implant of the same tumor. Invasion Metastasis 5, 295-308.
132. Kendal, W. S., and Frost, P. (1986). Metastatic potential and spontaneous mutation rates: Studies with two murine cell lines and their recently induced metastatic variants. Cancer Res. 46, 6131-6135.
133. Kendal, W. S., Wang, R.-Y., Hsu, T. C, and Frost, P. (1987). Rate of generation of major karyotypic abnormalities in relationship to the metastatic potential of B16 murine melanoma. Cancer Res. 47,3835-3841.
134. Kerbel, R. S., and Theodorescu, D. (1990). Tumor cell subpopulation interactions mediated by transforming growth factor β may contribute to clonal dominance of metastatically competent cells in primary tumors. In "Cell to Cell Interaction" (M. M. Burger, B. Sordat, and R. M. Zinkernagel, eds.), pp. 110-113. Karger, Basel.
135. Kerbel, R. S., Lagarde, A. E., Dennis, J. W., and Donaghue, T. P. (1983). Spontaneous fusion in vivo between normal host and tumor cells: Possible contribution to tumor progression and metastasis studied with a lectin-resistant tumor. Mol. Cell. Biol. 3, 523-538.
136. Kerbel, R. S., Frost, P., Liteplo, R., Carlow, D. A., and Elliott, B. E. (1984). Possible epigenetic mechanisms of tumor progression: Induction of high-frequency heritable but phenotypically unstable changes in the tumorigenic and metastatic properties of tumor cell populations by 5-azacytidine treatment. J. Cell. Pliysiol. Sitppl. 3, 87-97.
137. Kitchin, R. M., and Sager, R. (1980). Genetic analysis of tumorigenesis VI: Chromosome rearrangements in tumors derived from diploid premalignant Chinese hamster cells in nude mice. Somatic Cell Genet. 6, 615-630.
138. Konishi, N., Hiasa, Y., Matsuda, H., Tao, M., Tsuzuki, T., Hayashi, I., Kitahori, Y., Shiraishi, T., Yatani, R., Shimazaki, J., and Lin, I. C. (1995). Intratumor cellular heterogeneity and alterations in ras oncogene and p53 tumor suppressor gene in human prostate carcinoma. Am. J. Pathol. 147, 1112-1122.
139. Kripke, M. L., Gruys, E., and Fidler, I. J. (1978). Metastatic heterogeneity of cells from an ultraviolet light-induced murine fibrosarcoma of recent origin. Cancer Res. 38, 2962-2967.
140. Law, L. W. (1952). Origin of the resistance of leukemia cells to folic acid antagonists. Nature (London) 169, 628-629.
141. Leach, F. S., Nicolaides, N. C., Papadopoulos, N., Liu, B., Jan, J., Parsons, R., Peltomaki, P., Sistonen, P., Aaltonen, L. A., Nystro;u;m-Lahti, M., Guan, X. Y., Zhang, J., Meltzer, P. S., Yu, J. W., Kao, F. T., Chen, D. J., Cerosaletti, K. M., Fournrev, R. E. K., Todd, S., Lewis, T., Leach, R. J., Naylor, S. L., Weissenbach, J., Mecklin, J. P., Jarvinen, H., Peterson, G. M., Hamilton, S. R., Green, J., Jass, J., Watson, P., Lynch, H. T., Trent, J. M., de la Chapelle, A., Kinzler, K. W., and Vogelstein, B. (1993). Mutations of a MutS homolog in hereditary nonpolyposis colorectal cancer. Cell 75, 1215-1225.
142. Leith, J. T., and Michelson, S. (1990). Tumor radiocurability relationship to intrinsic tumor heterogeneity and to the tumor bed effect. Invasion Metastasis 10, 329-351.
143. Leith, J. T., Brenner, H. J., De Wyngaert, J. K., Dexter, D. L., Calabresi, P., and Glicksman, A. S. (1981)7 Selective modification of the X-ray response of two mouse mammary adenocar-cinoma sublines by N, N-dimethylformamidc. Int. J. Radiat, Oncol. Biol. Pliys. 7, 943-947.
144. Leith, J. T., Gaskins, L. A., Dexter, D. L., Calabresi, P., and Glicksman, A. S. (1982a). Alteration of the survival response of two human colon carcinoma subpopulations to X-irradiation by N, N-dimethylformamide. Cancer Res. 42, 30-34.
145. Leith, J. T., Dexter, D. L., DeWyngaert, J. K., Zeman, E. M., Chu, M. Y., Calabresi, P., and Glicksman, A. S. (1982b). Differential responses to x-irradiation of subpopulations of two heterogeneous human carcinomas in vitro. Cancer Res. 42, 2556-2561.
146. Leith, J. T., Heyman, P., DeWyngaert, J. K., Dexter, D. L., Calabresi, P., and Glicksman, A. S. (1983). Thermal survival characteristics of cell subpopulations isolated from a heterogeneous human colon tumor. Cancer Res. 43, 3240-3246.
147. Leith, J. T., Bliven, S. F., Lee, E. S., Glicksman, A. S., and Dexter, D. L. (1984). Intrinsic and extrinsic heterogeneity in the responses of parent and clonal human colon carcinoma xenografts to photon irradiation. Cancer Res. 44, 3757-3762.
148. Leith, J. T., Bliven, S. F., and Glicksman, A. S. (1985). Similarity of thermotolerance characteristics in heterogeneous human colon tumor subpopulations after exposure to fractionated heat doses (44°C). Radiat. Res. 104, 128-139.
149. Leith, J. T., Faulkner, L. E., Bliven, S. F., Michelson, S. (1988). Compositional stability of artificial heterogeneous tumors m vivo: use of mitomycin C as a cytotoxic probe. Cancer Res. 48, 2669-2673.
150. Li, J.-J., Oberlcy, L. W., St. Clair, D. K., Ridnour, L., and Oberley, T. D. (1995). Phenotypic changes induced in human breast cancer cells by overexpression of manganese-containing Superoxide dismutase. Oncogene 10, 1989-2000.
151. Lin, W.-C, O'Connor, K. L., and Culp, L. A. (1993). Complementation of two related tumor cell classes during experimental metastasis tagged with different histochemical marker genes. Br. J. Cancer 67, 910-921.
152. Ling, V., Chamber, A. F., Harris, J. F., and Hill, R. P. (1985). Quantitative genetic analysis of tumor progression. Cancer Metastasis Rev. 4, 173-194.
153. Linsley, P. S., Ochs, V., Horn, D., Ring, D. B., and Frankel, A. S. (1986). Heritable variation in expression of multiple tumor associated epitopes on a high molecular weight mucin-like antigen. Cancer Res. 46, 6380-6386.
154. Liteplo, R. G., and Kerbel, R. S. (1986). Periodate-oxidized adenosine induction of murine thymidine kinase: role of DNA methylation in the generation of tumor cell heterogeneity. Cancer Res. 46, 577-582.
155. Livingstone, L. R., White, A., Sprouse, J., Livanos, E., Jacks, T., and Tlsty, T. D. (1992). Altered cell cycle arrest and gene amplification potential accompany loss of wild-type p53. Cell 70, 923-935.
156. Ljungberg, B., Mehle, C., Sterling, R., and Roos, G. (1996). Heterogeneity in renal cell carcinoma and its impact on prognosis-A flow cytometric study. Br. J. Cancer 74, 123-127.
157. Loeb, L. A. (1991). Mutator phenotype may be required for multistage carcinogenesis. Cancer Res. 51, 3075-3079.
158. Loveless, S. E., and Heppner, G. H. (1983). Tumor-associated macrophages of mouse mammary tumors. J. Imnmnol. 131, 2074-2078.
159. Luria, S. E., and Delbrück, M. (1943). Mutations of bacteria from virus sensitivity to virus resistance. Genetics 28, 491-511.
160. Mackay, B., and Ordonez, N. G. (1993). Pathological evaluation of neoplasms with unknown primary tumor site. Semin. Oncol. 20, 206-228.
161. MacPhee, D. G. (1995). Mismatch repair, somatic mutations, and the origins of cancer. Cancer Res. 55, 5489-5492.
162. Mahoney, K. H., Miller, B. E., and Heppner, G. H. (1985). FACS quantitation of leucine aminopeptidase and acid phosphatase on tumor-associated macrophages from metastatic and nonmetastatic mouse mammary tumors. J. Leukocyte Biol. 38, 573-585.
163. Makino, S. (1956). Further evidence favoring the concept of the stem cell in ascite tumors of rats. Ann. NY Acad. Sci. 63, 818-830.
164. Malins, D. C., Polissar, N. L., and Gunselman, S. J. (1996). Progression of human breast cancers to the metastatic state is linked to hydroxyl radical-induced DNA damage. Proc. Nail. Acad. Sci. USA 93, 2557-2563.
165. Mantovani, A., Gravazzi, R., Allessandri, G., Spreafico, F., and Garattani, S. (1981). Characterization of tumor lines derived from spontaneous metastases of a transplanted murine sarcoma. Eur. J. Cancer 17, 71-76.
166. Markowitz, S., Wang, J., Mycroff, L., Parsons, R., Sung, L., Lutterbaugh, J., Fan, R. S., Zborowska, E., Kinzler, K. W., Vogelstein, B., Brattain, M., and Willson, J. K. V. (1995). Inactivation of the type II TGF-receptor in colon cancer cells with microsatellite instability. Science 268, 1336-1338.
167. Martin, F., Caignard, A., Jeannin, J. F., LeClerc, A., and Martin, M. (1983). Selection by trypsin of two sublines of rat colon cancer cells forming progressive or regressive tumors. Int. J. Cancer 32, 623-627.
168. McMillan, T. J., Kalebic, T., Stark, G. R., and Hart, I. R. (1990). High frequency of double drug resistance in the B16 melanoma cell line. Eur. J. Cancer 26, 565-567.
169. Meuth, M., L'Heureux-Huard, N., and Trudel, M. (1979). Characterization of a mutator gene in Chinese hamster ovary cells. Proc. Natl. Acad. Sci. USA 76, 6505-6509.
170. Meyer, J. S., and Wittliff, J. L. (1991). Beyond heterogeneity in breast carcinoma: Thymidine labelling index, steroid hormone receptors, DNA ploidy. Int. J. Cancer 47, 213-220.
171. Miller, B. E., Miller, F. R., Leith, J., and Heppner, G. H. (1980). Growth interaction in vivo between tumor subpopulations derived from a single mouse mammary tumor. Cancer Res. 40, 3977-3981.
172. Miller, B. E., Miller, F. R., and Heppner, G. H. (1981). Interactions between tumor subpopulations affecting their sensitivity to the antineoplastic agents cyclophosphamide and methotrexate. Cancer Res. 41, 4378-4381.
173. Miller, B. E., Miller, F. R., Wilburn, D., and Heppner, G. H. (1987). Analysis of tumour cell composition in tumours composed of paired mixtures of mammary tumour cell lines. Br. J. Cancer 56, 561-569.
174. Miller, B. E., Miller, F. R., Wilburn, D., and Heppner, G. H. (1988). Dominance of a tumor subpopulation line in mixed heterogeneous mouse mammary tumors. Cancer Res. 48, 5747-5753.
175. Miller, B. E., Miller, F. R., and Heppner, G. H. (1989). Therapeutic pertubution of the tumor ecosystem in reconstructed heterogeneous mouse mammary tumors. Cancer Res. 49, 3747-3753.
176. Miller, B. E., Machemer, T., Lehotan, M., and Heppner, G. H. (1991). Tumor subpopulation interactions affecting melphalan sensitivity in palpable mouse mammary tumors. Cancer Res. 51, 4378-4387.
177. Miller, B. E., Matherly, L. H., Lehotan, M., and Heppner, G. H. (1996). Rates of development of methotrexate resistance in heterogeneous mouse mammary tumor cell cultures. J. Exp. Ther. Oncol. 1, 30-38.
178. Miller, F. R. (1983). Tumor subpopulation interactions in metastasis. Invasion Metastasis 3, 234-242.
179. Miller, F. R., and Heppner, G. H. (1979). Immunologic heterogeneity of tumor cell subpopulations from a single mouse mammary tumor. JNCI, J. Natl. Cancer Inst. 63, 1457-1463.
180. Miller, F. R., and Heppner, G. H. (1990). Cellular interactions in metastasis. Cancer Metastasis Rev. 9, 21-34.
181. Miller, F. R., Miller, B. E., and Heppner, G. H. (1983). Characterization of metastatic heterogeneity among subpopulations of a single mouse mammary tumor: Heterogeneity in phenotypic stability. Invasion Metastasis 3, 22-31.
182. Miller, F. R., Mclnerney, D., Rogers, C, and Miller, B. E. (1988). Spontaneous fusion between metastatic mammary tumor subpopulations. /. Cell. Biochem. 36, 129-136.
183. Miller, F. R., Mohamed, A. N., and McEachern, D. (1989). Production of a more aggressive tumor cell variant by spontaneous fusion of two mouse tumor subpopulations. Cancer Res. 49, 4316-4321.
184. Miller, F. R., Soule, H. D., Tail, L., Pauley, R. J., Wolman, S. R., Dawson, P. J., and Heppner, G. H. (1993). Xenograft model of human proliferative breast disease. JNCI, J. Natl. Cancer Inst. 85, 1725-1732.
185. Mirchandani, D., Zheng, J., Miller, G. J., Ghosh, A. K., Shibata, D. K., Cote, R. J., and Roy-Burman, P. (1995). Heterogeneity in intratumor distribution of p53 mutations in human prostate cancer. Am. J. Patliol. 147, 92-101.
186. Mitelman, F. (1971). The chromosomes of fifty primary Rous rat sarcomas. Hereditas 69, 155-186.
187. Mitelman, F. (1972). Comparative chromosome analysis of primary and metastatic Rous sarcomas in rats. Hereditas 70, 1-14.
188. Moffett, B. F., Baban, D., Bao, L., and Tarin, D. (1992). Fate of clonal linkages during neoplasia and metastasis studied with an incorporated genetic marker. Cancer Res. 52, 1737-1743.
189. Moolten, F. L. (1986). Tumor chemosensitivity conferred by inserted herpes thymidine kinase genes: Paradigm for a prospective cancer control strategy. Cancer Res. 46, 5276-5281.
190. Nagase, F., Jamshedur-Rahman, S. M., Yokochi, T., Kawashima, K., Isobe, K.-I., Yoshida, T., Nagura, E.-I., and Nakashima, I. (1987). Dynamics of generation of antigen loss variants from L1210 murine leukemia clones detected by a tumor-specific T-cell clone. Cancer Res. 47, 6494-6499.
191. Nakashima, H., Inoue, H., Honda, M., Shibuta, K., Arinaga, S., Mori, M., Vee, H., Era, S., and Akiyoshi, T. (1995). The heterogeneity of microsatellite instability in multiple gastric cancers. Am. J. Gastroenterol. 90, 653-655.
192. Natali, P. G., Cavaliere, R., Bigotti, A., Nicotra, M. R., Russo, C, Ng, A. K., Giacomini, P., and Ferrone, S. (1983). Antigeneic heterogeneity of surgically removed primary and autologous metastatic human melanoma lesions. /. Immunol. 130, 1462-1466.
193. Newcomb, E., Silverstein, S. C., and Silagi, S. (1978). Malignant mouse melanoma cells do not form tumors when mixed with cells of a non-malignant subclone: Relationships between plasminogen activator expression by the tumor cells and the host's immune response. J. Cell. Physiol. 95, 169-178.
194. Nicolson, G. L., Brunson, K. W., and Fidler, I. J. (1978). Specificity of arrest, survival and growth of selected metastatic variant cell lines. Cancer Res. 38, 4105-4111.
195. Niederkorn, J. Y., and Streuen, J. N. (1983). Intracamerally induced concomitant immunity: mice harboring progressively growing intraocular tumors are immune to spontaneous metastases and secondary tumor challenge. J. Immunol 131, 2587-2594.
196. Noguchi, S., Matomura, K., Inaji, H., Imaoka, S., and Koyama, H. (1992). Clonal analysis of human breast cancer by means of the polymerase chain reaction. Cancer Res. 52, 6594-6597.
197. Nowell, P. C. (1976). The clonal evolution of tumor cell populations. Science 194, 23-28.
198. Nowotny, A., and Grohsman, J. (1973). Mixed tumor challenge of strain specific and nonspecific TA3 mouse ascites in mammary adenocarcinomas. Int. Arch. Allergy Appl. Immunol. 44, 434-440.
199. Ogawa, K., Soll, D. B., and Farber, E. (1980). Phenotypic diversity as an early property of putative preneoplastic hepatocyte populations in liver carcinogenesis. Cancer Res. 40, 725-733.
200. Okada, S., Ishii, H., Nose, H., Okusaka, T., Kyogoku, A., Yoshimori, M., Sakamoto, M., and Hirohashi, S. (1995). Intra-tumoral DNA heterogeneity of small hepatocellular carcinoma. Cancer 75, 444-450.
201. Okcu, A., Hofmann-Wellenhof, R., Woltsche, I., Smalle, J., and Kerl, H. (1996). Pathological findings suggestive of interclonal stabilization in a case of cutaneous melanoma. Clin. Exp. Metastasis 14, 215-218.
202. Olsson, L., and Ebesen, P. (1979). Natural polyclonality of spontaneous AKR leukemia and its consequences for so-called specific immunotherapy. JNCI, J. Natl. Cancer lust. 62, 623-627.
203. Olsson, L., and Forchhammer, J. (1984). Induction of the metastatic phenotype in a mouse tumor model by 5-azacytidine, and characterization of an antigen associated with metastatic activity. Proc. Natl. Acad, Sci. USA 81, 3389-3393.
204. Olsson, L., Sorcnscn, H. R., and Behinke, O. (1984). Intratumoral phenotypic diversity of cloned human lung tumor cell lines and consequences for analysis with monoclonal antibodies. Cancer 54, 1757-1765.
205. Olsson, L., Due, C., and Dumant, M. (1985). Treatment of human cell lines with 5-azacytidine may result in profound alterations in clonogenicity and growth rate./. Cell Biol. 100, 508-513.
206. Orndal, C, Rydholm, A., Willen, H., Mitelman, F., and Mandahl, N. (1994). Cytogenetic intratumor heterogeneity in soft tissue tumors. Cancer Genet. Cytogenet. 78, 127-137.
207. Paquette, B., and Little, J. B. (1994). In vivo enhancement of genomic instability in minisatellite sequences of mouse C3H/10T1/2 cells transformed in vitro by x-rays. Cancer Res. 54, 3173-3178.
208. Paradiso, A., Mangia, A., Barletta, A., Fusilli, S., Marzullo, F., Schittulli, F., and DeLena, M. (1995). Heterogeneity of intratumour proliferative activity in primary breast cancers: Biological and clinical aspects. Eur. J. Cancer 31A, 911-916.
209. Pierce, G., Aguilar, D., Hood, G., and Wells, R. S. (1984). Trophectoderm in control of murine embryonal carcinoma. Cancer Res. 44, 3987-3996.
210. Pierce, G. B., and Cox, W. F. (1978). Neoplasms as cariactures of tissue renewal. In "Cell Differentiation and Neoplasia" (G.F., Saunders, ed.), pp. 57-66. Raven Press, New York.
211. Pool, R. (1989). Is it healthy to be chaotic? Science 243, 604-607.
212. Posadas, E. M., Criley, S. R., and Coffey, D. S. (1996). Chaotic oscillations in cancer cells. Cancer Res. 56, 3682-3688.
213. Poste, G., and Grieg, R. (1982). On the genesis and regulation of cellular heterogeneity in malignant tumors. Invasion Metastasis 2, 137-176.
214. Poste, G., Doll, J., and Fidler, I. J. (1981). Interactions between clonal subpopulations affect the stability of the metastatic phenotype in polyclonal populations of B16 melanoma cells. Proc. Natl. Acad. Sci. USA 78, 6226-6230.
215. Poste, G., Tzeng, J., Doll, J., Grieg, R., Rieman, D., and Zeidman, I. (1982). Evolution of tumor cell heterogeneity during progressive growth of individual lung metastases. Proc. Nail. Acad. Sci. USA 79, 6574-6578.
216. Prehn, R. T. (1991). The inhibition of tumor growth by tumor mass. Cancer Res. 51, 2-4.
217. Price, J. E-, Bell, C., and Frost, P. (1990). The use of a genotypic marker to demonstrate clonal dominance during the growth and metastasis of a human breast carcinoma in nude mice. Int. J. Cancer 45, 968-971.
218. Radinsky, R., Kraemer, P. M., Proffitt, M. R., and Gulp, L. A. (1988). Clonal diversity of the Kirsten-ras oncogene during tumor progression in athymic nude mice: Mechanisms of amplification and rearrangement. Cancer Res. 48, 4941-4953.
219. Reid, T. M., and Loeb, L. A. (1992). Mutagenic specificity of oxygen radicals produced by human leukemia cells. Cancer Res. 52, 1082-1086.
220. Reynolds, T. Y., Rockwell, S., and Glazer, P. M. (1996). Genetic instability induced by the tumor microenvironment. Cancer Res. 56, 5754-5757.
221. Rhee, J. G., Schuman, V. L., Song, C. W., and Levitt, S. H. (1987). Difference in the thermotolerance of mouse mammary carcinoma cells in vivo and in vitro. Cancer Res. 47, 2571-2575.
222. Rice, G. C., Hoy, C., and Schimke, R. T. (1986). Transient hypoxia enhances the frequency of dihydrofolate reductase gene amplification in Chinese hamster ovary cells. Proc. Natl. Acad. Sci. USA 83, 5978-5982.
223. Rideout, W. M., Coetzec, G. A., Olumi, A. F., and Jones, P. A. (1990). 5-Methycytosine as an endogenous mutagen in the human LDL receptor and p53 genes. Science 249, 1288-1290.
224. Robinson, S. P., and Jordan, V. C. (1989). Antiestrogenic action of toremifene on hormonedependent, -independent, and heterogeneous breast tumor growth in the athymic mouse. Cancer Res. 49, 1758-1762.
225. Rodriguez, E., Sreekantaiah, C, and Chaganti, R. S. K. (1994). Genetic changes in epithelial tumors. Cancer Res. 54, 3398-3406.
226. Rofstad, E. K. (1992). Radiation sensitivity in vitro of primary tumors and metastatic lesions of malignant melanoma. Cancer Res. 52, 4453-4457.
227. Rosin, M. P., Anwar, W. A., and Ward, A. J. (1994). Inflammation, chromosomal instability, and cancer: The schistomiasis model. Cancer Res. 54, 1929s-1933s.
228. Rosowsky, A., Wright, J. E., Cucchi, C. A., Lippke, J. A., Tantravahi, R., Ervin, T. J., and Frei, E., 3rd (1985). Phenotypic heterogeneity in cultured human head and neck squamous cell carcinoma lines with low-level methotrexate resistance. Cancer Res. 45, 6205-6212.
229. Roth, J. A., Restrepo, C, Scuderi, P., Baldwin, R. W., Reichert, C. M., and Hosoi, S. (1984). Analysis of antigenic expression by primary and autologous metastatic human sarcomas using murine monoclonal antibodies. Cancer Res. 44, 5320-5325.
230. Roth, J. A., Nguyen, D., Lawrence, D. D., Kemp, B. L., Carrasco, C. H., Person, D. Z., Hong, W. K., Kemaki, R., Lee, J. J., Nesbitt, J. C, Pisters, K. M. W., Putnam, J. B., Schea, R., Shin, D. M., Walsh, G. L., Dolormente, M. M., Han, C.-I., Martin, F. D., Yen, N., Xu, K., Stephens, L. C, McDonnell, T. J., Mukhopadhyay, T., and Cai, D. (1996). Retrovirus-mediated wild-type p53 gene transfer to tumor of patients with lung cancer. Nature Med. 2, 985-991.
231. Rubin, A. L., Yao, A., and Rubin, H. (1990). Relation of spontaneous transformation in cell culture to adaptive growth and clonal heterogeneity. Proc. Natl. Acad. Sci. USA 87, 482-486.
232. Rubin, A. L., Sneade-Koenig, A., and Rubin, H. (1992). High rate of diversification and reversal among subclones of neoplastically transformed N1H 3T3 clones. Proc. Natl. Acad. Sci. 1/5/189, 4183-4186.
233. Rubin, H. (1988). Uniqueness of each spontaneous transformant from a clone of BALB/c 3T3 cells. Cancer Res. 48, 2512-2518.
234. Rubin, H. (1994a). Epigenetic nature of neoplastic transformation. In "Developmental Biology and Cancer, " pp. 61-84. CRC Press, Boca Raton, FL.
235. Rubin, H. (1994b). Experimental control of neoplastic progression in cell populations: Fould's rules revisited. Proc. Natl. Acad. Sci. USA 91, 6619-6623.
236. Rubin, H., and Xu, K. (1989). Evidence for the progressive and adaptive nature of spontaneous transformation in the NIH 3T3 cell line. Proc. Natl. Acad. Sci. USA 86, 1860-1864.
237. Rubin, H., Arnstein, P., and Chu, B. M. (1984). High-frequency variation and population drift in a newly transformed clone of Balb/c/3T3 cells. Cancer Res. 44, 5242-5248.
238. Rubin, H., Hennessey, T. L., Sanui, H., Arnstein, P., Taylor, D. O. N., and Chu, B. B. (1985). Inheritance of acquired changes in growth capacity of spontaneously transformed BALE/3T3 cells propagated in mice and culture. Cancer Res. 45, 2550-2559.
239. Rudland, P. S., Gusterson, B. A., Hughes, C. M., Omerod, E. J., and Warburton, M. J. (1982). Two forms of tumors in nude mice generated by a neoplastic rat mammary stem cell line. Cancer Res. 42, 5196-5208.
240. Samiei, M., and Waghorne, C. (1991). Clonal selection within metastatic SPI mouse mammary tumors is independent of metastatic potential. Int. J. Cancer 47, 771-775.
241. Sasaki, O., Soejima, K., and Haraguchi, Y. (1993). DNA ploidy in undiffentiated carcinomas of the human stomach-With special reference to its heterogeneity and the relation between its intratumor distribution pattern and prognosis. In Vivo 7, 363-368.
242. Schapers, R., Smects, W., Hopman, A., Pauwels, R., Geraedts, J., and Ramaekers, F. (1993). Heterogeneity in bladder cancer as detected by conventional chromosome analysis and interphase cytogenetics. Cancer Genet. Cytogenet. 70, 56-61.
243. Schimke, R. T., Hill, A., and Johnston, R. N. (1985). Methotrexate resistance and gene amplification: An experimental model of tumor heterogeneity. Br. J. Cancer 51, 459-465.
244. Schlag, P., and Schreml, W. (1982). Heterogeneity in growth pattern and drug sensitivity of primary tumor and metastases in the human tumor colony-forming assay. Cancer Res. 42, 4086-4089.
245. Schlappack, O. K., Zimmerman, A., and Hill, R. P. (1991). Glucose starvation and acidosis: Effect on experimental metastatic potential, DNA content and MTX resistance of murine tumor cells. Br. J. Cancer 64, 663-670.
246. Schnipper, L. E. (1986). Clinical implications of tumor-cell heterogeneity. N. Engl- J. Med. 314, 1423-1431.
247. Schvimer, M., Lash, R. H., and Katzin, W. E. (1995). Intratumoral heterogeneity of DNA ploidy in breast carcinomas: A flow cytometric assessment of sampling techniques. Cytometry 22, 292-296.
248. Seshadri, R., Kutlaca, R. J., Trainor, K., Matthews, C, and Morley, A. A. (1987). Mutation rate of normal and malignant human lymphocytes. Cancer Res. 47, 407-409.
249. Shankey, T. V., Jin, J.-K., Dougherty, S., Flanigan, R. C, Graham, S., and Pyle, J. M. (1995a). DNA ploidy and proliferation heterogeneity in human prostate cancers. Cylomelry 21, 30-39.
250. Shankey, T. V., Jin, J.-K., Flanigan, R. C, and Pyle, J. M. (1995b). Analysis of heterogeneity in human tumors. Cylomelry 22, 159-160.
251. Shibeta, D., Schaeffer, J., Li, Z.-H., Capella, G., and Perucho, M. (1993). Genetic heterogeneity of the c-k-ras locus in colorectal adenomas but not in adenocarcinomas. JNCI, J. Natl. Cancer Inst. 85, 1058-1063.
252. Shirasuna, K., Watani, K., Sugiyama, M., Marioka, S., and Miyazaki, T. (1986). Isolation and characterization of different clones including myoepithelial-like variants from a clonal neoplastic epithelial duct cell line of human salivary gland origin. Cancer Res. 46, 1418-1426.
253. Siitonen, S. M., Isola, J. J., Rantala, I. S., and Heiin, H. J. (1993). Intratumor variation in cell proliferation in breast carcinoma as determined by antiproliferating cell nuclear antigen monoclonal antibody and automated image analysis. Am. J. Clin. Patliol. 99, 226-231.
254. Simmons, W. F., Liu, J., Knowles, D. M., and Inghirami, G. (1995). Breast cancer heterogeneity: evaluation of clonality in primary and metastatic lesions. Hum. Patliol. 26, 210-216.
255. Siracky, J. (1979). An approach to the problem of heterogeneity of human tumour cell populations. Br. J. Cancer 39, 570-577.
256. Slocum, H. K., Heppner, G. H., and Rustum, Y. M. (1985). Cellular heterogeneity of human tumors. Biol. Responses Cancer 4, 183-248.
257. Smeds, S., Peter, H. J., Jortso, E., Gerber, H., and Studer, H. (1987). Naturally occurring clones of cells with high intrinsic proliferation potential within the follicular epithelium of mouse thyroids. Cancer Res. 47, 1646-1651.
258. Sonnenberg, A., Daams, H., Calafat, J., and Hilgers, J. (1986). In vitro differentiation and progression of mouse mammary tumor cells. Cancer Res. 46, 5913-5922.
259. Staroselsky, A., Pathak, S., and Fidler, I. J. (1990). Changes in clonal composition during in vivo growth of mixed subpopulations derived from the murine K-1735 melanoma. Anticancer Res. 10, 291-296.
260. Staroselsky, A. N., Radinsky, R., Fidler, I. J., Pathak, S., Chernajovsky, Y., and Frost, P. (1992). The use of molecular genetic markers to demonstrate the effect of organ environment on clonal dominance in a human renal-cell carcinoma grown in nude mice. Int. J. Cancer 51, 130-138.
261. Stoler, D. L., Anderson, G. R., Russo, C. A., Spina, A. M., and Beerman, T. A. (1992). Anoxia-inducible endonuclease activity as a potential basis of the genomic instability of cancer cells. Cancer Res. 52, 4372-4378.
262. Szatrowski, T. P., and Nathan, C. F. (1991). Production of large amounts of hydrogen peroxide by human tumor cells. Cancer Res. 51, 794-798.
263. Takahashi, Y., Takenada, A., Ishiguro, T., and Noda, Y. (1994). Intratumoral DNA heterogeneity correlated with lymph node involvement and surgical staging in epithelial ovarian cancer by flow cytometry. Cancer 73, 3011-3014.
264. Talmadge, J., Wolman, S. R., and Fidler, I. J. (1982). Evidence for the clonal origin of spontaneous metastases. Science 217, 361-363.
265. Talmadge, J. E., Benedict, K., Madsen, J., and Fidler, I. J. (1984). Development of biological diversity and susceptibility to chemotherapy in murine cancer metastases. Cancer Res. 44, 3801-3805.
266. Tanigawa, N., Mizuno, Y., Hashimura, T., Honda, K., Satomura, K., Hikasa, Y., Niwa, O., Sugahara, T., Yoshida, O., Kern, D. H., and Morton, D. L. (1984). Comparison of drug sensitivity among tumor cells within a tumor, between primary tumor and metastases, and between different metastases in the human tumor colony-forming assay. Cancer Res. 44, 2309-2312.
267. Tanooka, H. (1988). Monoclonal growth of cancer cells: experimental evidence. Jpn. J. Cancer Res. 79, 657-665.
268. Tanooka, H., and Tanaka, K. (1982). Evidence for single-cell origin of 3-methylcholanthrene-induced fibrosarcomas in mice with cellular mosaicism. Cancer Res. 42, 1856-1858.
269. Teixeira, M. R., Pandis, N., Bardi, G., Andersen, N., Mandahl, N., Mitelman, F., and Heim, S. (1994). Cytogenetic analysis of multifocal breast carcinomas: Detection of karyotypically unrelated clones as well as clonal similarities between tumour foci. Br. J. Cancer 70, 922-927.
270. Teixeira, M. R., Pandis, N., Bards, G., Anderson, J. A., Mitelman, F., and Heim, S. (1995). Clonal heterogeneity in breast cancer: Karyotypic comparisons of multiple intra- and extra-tumorous samples from 3 patients. Int. J. Cancer 63, 63-68.
271. Teixeira, M. R., Pandis, N., Bardi, G., Andersen, J. A., and Heim, S. (1996). Karyotypic comparisons of multiple tumorous and macroscopically normal surrounding tissue samples from patients with breast cancer. Cancer Res. 56, 855-859.
272. Tlsty, T. D. (1990). Normal diploid human and rodent cells lack a detectable frequency of gene amplification. Proc. Natl. Acad. Sci. USA 87, 3132-3136.
273. Tlsty, T. D., Margolin, B. H., and Lum, K. (1989). Differences in the rates of gene amplification in nontumorigenic and tumorigenic cell lines as measured by Luria-Delbriick fluctuation analysis. Proc. Natl. Acad. Sci. USA 86, 9441-9445.
274. Tofilon, P., Buckley, N., and Deen, D. F. (1984). Effect of cell-cell interactions on drug sensitivity and growth of drug sensitive and-resistant tumor cells in spheroids. Science 226, 862-864.
275. Tomasovic, S. P., Rosenblatt, P. L., Johnston, D. A., Tang, K., and Lee, P. S. Y. (1984). Heterogeneity in induced host resistance and its relation to synthesis of stress proteins in rat tumor cell clones. Cancer Res. 44, 5850-5856.
276. Tomlinson, I. P. M., Novelli, M. R., and Bodmer, W. F. (1996). The mutation rate and cancer. Proc. Natl. Acad. Sci. USA 93, 14800-14803.
277. Trope, C., Aspergen, K., Kullander, S., and Astedt, B. (1979). Heterogeneous response of disseminated human ovarian cancers to cytostatics in vitro. Acta Obstet. Gynecol. Scand. 58, 543-546.
278. Trosko, J. E., Jone, C, and Chang, C. C. (1983). The role of tumor promoters on phenotypic alterations affecting intercellular communication and tumorigenesis. Ann. NY Acad. Sci. 407, 316-327.
279. Tsuruo, T., and Fidler, I. J. (1981). Differences in drug sensitivity among tumor cells from parental tumors, selected variants, and spontaneous metastases. Cancer Res. 41, 3058-3064.
280. Van der Poel, H. G., Mulders, P. F. A., Oosterhof, G. D. N., Schaafsma, H. E., Hendriks, J. C. M., Schalken, J. A., and Debruyne, F. M. J. (1993). Prognostic value of karyometric and clinical characteristics in renal cell carcinoma. Cancer 72, 2667-2674.
281. Varani, J., Orr, W., and Ward, P. A. (1978). A comparison of the migration patterns of normal and malignant cells in two assay systems. Am. J. Patlwl. 90, 159-172.
282. Vaupel, P., Kallinowski, F., and Okunieff, P. (1989). Blood flow, oxygen and nutrient supply, and metabolic microenvironment of human tumors: A review. Cancer Res. 49, 6449-6465.
283. Visscher, D., Dblan, P., Ottosen, S., and Crissman, J. (1995). Geographic distribution of codominant DNA stemlines in breast carcinomas. Cyiomeiry 21, 14-17.
284. Vogelstein, B., Fearon, F. E., Hamilton, S. R., and Feinberg, A. P. (1985). Use of restriction fragment length polymorphism to determine the clonal origin of human tumors. Science 227, 642-645.
285. Volpc, J. P., and Milas, L. (1988). Metastatic instability of murine tumor metastases: Dependence on tumor type. Clin. Exp. Metastasis 6, 333-346.
286. von Hoff, D. D. (1985). Implications of tumor cell heterogeneity for in vitro drug sensitivity testing. Semin. Oncol. 12, 327-331.
287. von Hoff, D. D., Clark, G. M., Forseth, B. J., and Cowan, J. D. (1986). Simultaneous in vitro drug sensitivity testing on tumor from different sites in the same patient. Cancer 58, 1007-1013.
288. Waghorne, C., Thomas, M., Lagarde, A., Kerbel, R. S., and Breitman, M. L. (1988). Genetic evidence for progressive selection and overgrowth of primary tumors by metastatic cell populations. Cancer Res. 48, 6109-6114.
289. Wallen, C. A., Ridinger, D. N., and Dethlefson, L. A. (1985). Heterogeneity of x-ray cytoxicity in proliferating and quiescent murine mammary carcinoma cells. Cancer Res. 45, 3064-3069.
290. Wang, N., Yu, S. H., Liener, I. E., Hebbel, R. P., Eaton, J., and McKhann, C. F. (1982). Characterization of high-and-Iow -metastatic clones derived from a methylcholanthrene-induced murine fibrosarcoma. Cancer Res. 42, 1046-1051.
291. Warzynski, M. J., Soechtig, C. E., Maatman, T. J., Goldsmith, L. C., Grobbel, M. A., Carothers, C. G., and Shockley, K. F. (1995). DNA heterogeneity determined by flow cytometry in prostatic adenocarcinoma-necessitating multiple site analysis. Prostale 27, 329-335.
292. Weiss, P.A. (1973). "The Science of Life." Futura Publications, Mt. Kisco, NY.
293. Weitzman, S. A., and Stossel, T. P. (1981). Mutation caused by human phagocytes. Science 212, 546-547.
294. Weitzman, S. A., and Stossel, T. P. (1982). Effects of oxygen radical scavengers and antioxidants on phagocyte-induced mutagenesis. J. Immunol. 128, 2770-2772.
295. Weitzman, S. A., Weitberg, A. B., Clark, E. P., and Stossel, T. P. (1985). Phagocytes as carcinogens: Malignant transformation produced by human neutrophils. Science 227, 1231-1233.
296. Welch, D. R., and Nicolson, G. L. (1983). Phenotypic drift and heterogeneity in response of metastatic mammary adenocarcinoma cell clones to Adriamycin, 5-fluro-2-deoxyuridine and methotrexate treatment in vitro. Clin. Exp. Metastasis 1, 317-325.
297. Welch, D. R., Milas, L., Tomasovic, S. P., and Nicholson, G. L. (1983). Heterogeneous response and clonal drift of sensitivities of metastatic 13762NF mammary adenocarcinoma clones to gamma radiation in vitro. Cancer Res. 43, 6-10.
298. Welch, D. R., Krizman, D. B., and Nicolson, G. (1984a). Multiple phenotypic divergence of mammary adenocarcinoma cell clones. I In vitro and in vivo properties. Clin. Exp. Metastasis 2, 333-355.
299. Welch, D. R., Evans, D. P., Tomasovic, S. P., Milas, L., and Nicolson, G. L. (1984b). Multiple phenotypic divergence of mammary adenocarcinoma cell clones. II. Sensitivity to radiation, hyperthermia and FUdR. Clin. Exp. Metastasis 2, 357-371.
300. i in single heart cells revealed by Fura-2. Science 235, 325-328.
301. Wikstrand, D. J., Bigner, S. H., and Bigner, D. D. (1983). Demonstration of complex antigenic heterogeneity in a human glioma cell line and eight derived clones by specific monoclonal antibodies. Cancer Res. 43, 3327-3334.
302. Wilson, M. S., West, C. M. L., Wilson, G. D., Roberts, S. A., James, R. D., and Schofield, P. F. (1993). Intra-tumoral heterogeneity of tumour potential doubling times (Tpot) in colorectal cancer. Br. J. Cancer 68, 501-506.
303. Wolman, S. R., McMorrow, L. E., Fidler, I. J., and Talmadge, J. E. (1985). Development and progression of karyotypic variability in melanoma K1735 following x-irradiation. Cancer Res. 45, 1839-1844.
304. Wong, G. H., and Goeddel, D. V. (1988). Induction of manganous Superoxide dismutase by tumor necrosis factors: Possible protective mechanism. Science 242, 941-943.
305. Woo, S. Y., Anderson, R. L., Kapp, D. S., Kerson, I. V., Rice, G. C, Krag, D. N., and Hahn, G. M. (1991). Heterogeneity of heat response in murine, canine and human tumors: influence on predictive assays. Int. J. Racijat. Oncol. Biol. Pliys. 20, 479-488.
306. Woodruff, M. F. A., Ansell, J. D., Forbes, G. M., Gordon, J. C, and Micklem, H. S. (1982). Clonal interaction in tumors. Nature (London) 229, 822-824.
307. Yamashina, K., and Heppner, G. H. (1985). Correlation of frequency of induced mutation and metastatic potential in tumor cell lines from a single mouse mammary tumor. Cancer Res. 45, 4015-4019.
308. Yamashina, K., Miller, B. E., and Heppner, G. H. (1986). Macrophage-mediated induction of drug resistant variants in a mouse mammary tumor cell line. Cancer Res. 46,2396-2401.
309. Yao, A., Rubin, A. L., and Rubin, H. (1990). Progressive state selection of cells in low serum promotes high density growth and neoplastic transformation in NIH 3T3 cells. Cancer Res. 50, 5171-5176.
310. Yee, C. Y., Roodi, N., Verrier, C. S., and Pari, F. F. (1994). Microsatellite instability and loss of heterozygosity in breast cancer. Cancer Res. 54,1641-1644.
311. Yildiz, I., Jaffe, N., Aksoy, F., and El-Naggar, A. K. (1994). Regional DNA content heterogeneity in Wilm's Tumor: Incidence and potential clinical relevance. Anticancer Res. 14,1365-1370.
312. Yin, Y., Tainsky, M. A., Bischoff, F. Z., Strong, L. C, and Wahl, G. M. (1992). Wild-type p53 restores cell cycle control and inhibits gene amplification in cells with mutant p53 alleles. Cell 70, 737-748.
313. Yokoyama, A., Muramatsu, T., Ohmori, T., Makuuchi, H., Higuchi, S., Matsushita, S., Yoshino, K., Maruyama, K., Nakano, M., and Ishii, H. (1996). Multiple primary esophageal and concurrent upper aerodigestive tract cancer and the aldehyde dehydrogenase-2 genotype of Japanes alcoholics. Cancer 77, 1986-1990.
314. Young, S. D., and Hill, R. P. (1988). Hypoxia induces DNA overreplication and enhances metastatic potential of murine tumor cells. Proc. Natl. Acad. Sci. USA 85, 9533-9537.
315. Young, S. D., and Hill, R. P. (1990a). Effects of reoxygenation on cells from hypoxic regions of solid tumors: Anticancer drug sensitivity and metastatic potential. JNCI, J. Natl. Cancer lust. 82, 371-380.
316. Young, S. D., and Hill, R. P. (1990b). Effects of reoxygenation on cells from hypoxic regions of solid tumors: analyses of transplanted murine tumors for evidence of DNA overreplication. Cancer Res. 50, 5031-5038.
317. Yung, W.-K. A., Shapiro, J. R., and Shapiro, W. R. (1982). Heterogeneous chemosensitivities of subpopulations of human glioma cells in culture. Cancer Res. 42, 992-998.
318. Zhang, X.-H., and Xie, T.-X. (1995). Heterogeneity of malignant tumors should be considered when performing flow cytometric DNA analysis. Cytometry 22, 158-159.
319. Zhou, G.-H. K., Secrist, G. L., Brattain, M. G., and Mulder, K. M. (1995). Clonal heterogeneity of the sensitivity of human colon carcinoma cell lines to TGF isoforms. J. Cell. Physiol. 165, 512-520.