Low-frequency loss of heterozygosity in moloney murine leukemia virus- induced tumors in BRAKF1/J mice

Journal of Virology

Volumn 71, Issue 5, 1997, Pages 3940-3952

  Lander, Jeffrey K ^a   Fan, Hung ^a,b  

^a UNIVERSITY OF CALIFORNIA   (United States)

^b UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANIMAL CELL; ARTICLE; CHROMOSOME 4; FEMALE; GENE INSERTION; HETEROZYGOSITY; HUMAN; LEUKEMIA; LEUKEMOGENESIS; MALE; MOLONEY LEUKEMIA ONCOVIRUS; MOUSE; PRIORITY JOURNAL; TUMOR SUPPRESSOR GENE;

EID: 0031001925     PISSN: 0022538X     EISSN: None     Source Type: Journal    
DOI: 10.1128/jvi.71.5.3940-3952.1997     Document Type: Article

References (96)

1. Baxter, E. W., K. Blyth, L. A. Donehower, E. R. Cameron, D. E. Onions, and J. C. Neil. 1996. Moloney murinc leukemia virus-induced lymphomas in p53-deficient mice: overlapping pathways in tumor development? J. Virol. 70:2095-2100.
2. Ben-David, Y., and A. Bernstein. 1991. Friend virus-induced erythroleukemia and the multistage nature of cancer. Cell 66:831-834.
3. Ben-David, Y., A. Lavigueur, G. Y. Cheong, and A. Bernstein. 1990. Insertional inactivation of the p53 gene during Friend leukemia: a new strategy for identifying tumor suppressor genes. New Biol. 2:1015-1023.
4. Bergeron, D., J. Houde, L. Poliquin, B. Barbeau, and E. Rassart. 1993. Expression and DNA rearrangement of proto-oncogenes in Cas-Br-E-induced non-T-, non-B-cell leukemias. Leukemia 7:954-962.
5. Brightman, B. K., K. G. Chandy, R. H. Spencer, S. Gupta, P. K. Pattengale, and H. Fan. 1988. Characterization of lymphoid tumors induced by a recombinant murine retrovirus carrying the avian v-myc oncogene. Identification of novel (B-lymphoid) tumors in the thymus. J. Immunol. 141:2844-2854.
6. Brightman, B. K., A. Rein, D. J. Trepp, and H. Fan. 1991. An enhancer variant of Moloney murine leukemia virus defective in leukemogenesis does not generate detectable mink cell focus-inducing virus in vivo. Proc. Natl. Acad. Sci. USA 88:2264-2268. (Erratum, 88:5066.)
7. Cannon-Albright, L. A., D. E. Goldgar, L. J. Meyer, C. M. Lewis, D. E. Anderson, J. W. Fountain, M. E. Hegi, R. W. Wiseman, E. M. Petty, and A. E. Bale. 1992. Assignment of a locus for familial melanoma, MLM, to chromosome 9p13-p22. Science 258:1148-1152.
8. Chaillet, J. R. 1994. Genomic imprinting: lessons from mouse transgenes. Mutat. Res. 307:441-449.
9. Cloyd, M. W., J. W. Hartley, and W. P. Rowe. 1980. Lymphomagenicity of recombinant mink cell focus-inducing murine leukemia viruses. J. Exp. Med. 151:542-552.
10. Cornelisse, C. J., N. Kuipers-Dijkshoorn, M. van Vliet, J. Hermans, and P. Devilee. 1992. Fractional allelic imbalance in human breast cancer increases with tetraploidization and chromosome loss. Int. J. Cancer 50:544-548.
11. Cuypers, H. T., G. Selten, W. Quint, M. Zijlstra, E. R. Maandag, W. Boelens, P. van Wezenbeek, C. Melief, and A. Berns. 1984. Murine leukemia virus-induced T-cell lymphomagenesis: integration of proviruses in a distinct chromosomal region. Cell 37:141-150.
12. Cuypers, H. T., G. C. Selten, M. Zijlstra, R. E. de Goede, C. J. Melief, and A. J. Berns. 1986. Tumor progression in murine leukemia virus-induced T-cell lymphomas: monitoring clonal selections with viral and cellular probes. J. Virol. 60:230-241.
13. Davis, B. R., E. Linney, and H. Fan. 1985. Suppression of leukaemia virus pathogenicity by polyoma virus enhancers. Nature 314:550-553.
14. Dietrich, W. F., J. Miller, R. Steen, M. A. Merchant, D. Damron-Boles, Z. Husain, R. Dredge, M. J. Daly, K. A. Ingalls, T. J. O'connor, C. A. Evans, M. M. DeAngelis, D. M. Levinson, L. Kruglyak, N. Goodman, N. G. Copeland, N. A. Jenkins, T. L. Hawkins, L. Stein, D. C. Page, and E. S. Lander. 1996. A comprehensive genetic map of the mouse genome. Nature 380:149-152.
15. Dietrich, W. F., E. H. Radany, J. S. Smith, J. M. Bishop, D. Hanahan, and E. S. Lander. 1994. Genome-wide search for loss of heterozygosity in transgenic mouse tumors reveals candidate tumor suppressor genes on chromosomes 9 and 16. Proc. Natl. Acad. Sci. USA 91:9451-9455.
16. Dreyfus, F., B. Sola, S. Fichelson, P. Varlet, M. Charon, P. Tambourin, F. Wendling, and S. Gisselbrecht. 1990. Rearrangements of the Pim-1, c-myc, and p53 genes in Friend helper virus-induced mouse erythroleukemias. Leukemia 4:590-594.
17. Evans, L. H., and M. W. Cloyd. 1985. Friend and Moloney murine leukemia viruses specifically recombine with different endogenous retroviral sequences to generate mink cell focus-forming viruses. Proc. Natl. Acad. Sci. USA 82: 459-463.
18. Evans, L. H., and F. G. Malik. 1987. Class II polytropic murine leukemia viruses (MuLVs) of AKR/J mice: possible role in the generation of class I oncogenic polytropic MuLVs. J. Virol. 61:1882-1892.
19. Evans, L. H., and J. D. Morrey. 1987. Tissue-specific replication of Friend and Moloney murine leukemia viruses in infected mice. J. Virol. 61:1350-1357.
20. Fan, H. 1990. Influences of the long terminal repeats on retrovirus pathogenicity. Semin. Virol. 1:165-174.
21. Fan, H. 1994. Retroviruses and their role in cancer, p. 313-362. In J. A. Levy (ed.), The Retroviridae. Plenum Press, New York, N.Y.
22. Fan, H., H. Chute, E. Chao, and P. K. Pattengale. 1988. Leukemogenicity of Moloney murine leukemia viruses carrying polyoma enhancer sequences in the long terminal repeat is dependent on the nature of the inserted polyoma sequences. Virology 166:58-65.
23. Fearon, E. R., and B. Vogelstein. 1990. A genetic model for colorectal tumorigenesis. Cell 61:759-767.
24. Feuerman, M. H., B. R. Davis, P. K. Pattengale, and H. Fan. 1985. Generation of a recombinant Moloney murine leukemia virus carrying the v-src gene of avian sarcoma virus: transformation in vitro and pathogenesis in vivo. J. Virol. 54:804-816.
25. Feuerman, M. H., W. T. Lee, P. K. Pattengale, and H. Fan. 1988. Comparison of three recombinant murine leukemia viruses carrying the v-src oncogene of avian sarcoma virus: differences in in vitro transformation and in vivo pathogenicity. Mol. Carcinog. 1:57-66.
26. Flug, F., P. G. Pelicci, F. Bonetti, D. M. Knowles, and R. Dalla-Favera. 1985. T-cell receptor gene rearrangements as markers of lineage and clonality in T-cell neoplasms. Proc. Natl. Acad. Sci. USA 82:3460-3464.
27. Fountain, J. W., M. Karayiorgou, M. S. Ernstoff, J. M. Kirkwood, D. R. Vlock, L. Titus-Ernstoff, B. Bouchard, S. Vijayasaradhi, A. N. Houghton, J. Lahti, V. J. Kidd, D. E. Housman, and N. C. Dracopoli. 1992. Homozygous deletions of human chromosome 9p21 in melanoma. Proc. Natl. Acad. Sci. USA 89:10557-10561.
28. Frankel, W. N. 1995. Personal communication.
29. Frankel, W. N., J. P. Stoye, B. A. Taylor, and J. M. Coffin. 1989. Genetic analysis of endogenous xenotropic murine leukemia viruses: association with two common mouse mutations and the viral restriction locus Fv-1. J. Virol. 63:1763-1774.
30. Frankel, W. N., J. P. Stoye, B. A. Taylor, and J. M. Coffin. 1990. A linkage map of endogenous murine leukemia proviruses. Genetics 124:221-236. (Erratum, 125:455.)
31. Geiser, A. G., and E. J. Stanbridge. 1989. A review of the evidence for tumor suppressor genes. Crit. Rev. Oncog. 1:261-276.
32. Gonzalez-Zulueta, M., C. M. Bender, A. S. Yang, T. Nguyen, R. W. Beart, J. M. Van Tornout, and P. A. Jones. 1995. Methylation of the 5′ CpG island of the p16/CDKN2 tumor suppressor gene in normal and transformed human tissues correlates with gene silencing. Cancer Res. 55:4531-4535.
33. Graham, M., J. M. Adams, and S. Cory. 1985. Murine T lymphomas with retroviral inserts in the chromosomal 15 locus for plasmacytoma variant translocations. Nature 314:740-743.
34. Harris, H. 1988. The analysis of malignancy by cell fusion: the position in 1988. Cancer Res. 48:3302-3306.
35. Hartley, J. W., N. K. Wolford, L. J. Old, and W. P. Rowe. 1977. A new class of murine leukemia virus associated with development of spontaneous lymphomas. Proc. Natl. Acad. Sci. USA 74:789-792.
36. Hayward, W. S., B. G. Neel, and S. M. Astrin. 1981. Activation of a cellular one gene by promoter insertion in ALV-induced lymphoid leukosis. Nature 290:475-480.
37. Hebert, J., J. M. Cayuela, J. Berkeley, and F. Sigaux. 1994. Candidate tumor-suppressor genes MTS1 (p16INK4A) and MTS2 (p15INK4B) display frequent homozygous deletions in primary cells from T-but not from B-cell lineage acute lymphoblastic leukemias. Blood 84:4038-4044.
38. Hedrick, S. M., D. I. Cohen, E. A. Nielsen, and M. M. Davis. 1984. Isolation of cDNA clones encoding T cell-specific membrane-associated proteins. Nature 308:149-153.
39. Hegi, M. E., T. R. Devereux, W. F. Dietrich, C. J. Cochran, E. S. Lander, J. F. Foley, R. R. Maronpot, M. W. Anderson, and R. W. Wiseman. 1994. Allelotype analysis of mouse lung carcinomas reveals frequent allelic losses on chromosome 4 and an association between allelic imbalances on chromosome 6 and K-ras activation. Cancer Res. 54:6257-6264.
40. Herzog, C. R., R. W. Wiseman, and M. You. 1994. Deletion mapping of a putative tumor suppressor gene on chromosome 4 in mouse lung tumors. Cancer Res. 54:4007-4010.
41. Huang, D. P., K. W. Lo, C. A. van Hasselt, J. K. Woo, P. H. Choi, S. F. Leung, S. T. Cheung, P. Cairns, D. Sidransky, and J. C. Lee. 1994. A region of homozygous deletion on chromosome 9p21-22 in primary nasopharyngeal carcinoma. Cancer Res. 54:4003-4006.
42. Ichimura, K., E. E. Schmidt, N. Yamaguchi, C. D. James, and V. P. Collins. 1994. A common region of homozygous deletion in malignant human gliomas lies between the IFN alpha/omega gene cluster and the D9S171 locus. Cancer Res. 54:3127-3130.
43. Jackson Laboratory. 1991. Handbook on genetically standardized JAX mice, p. 6. The Jackson Laboratory, Bar Harbor, Maine.
44. Johnson, P., and S. Benchimol. 1992. Friend virus induced murine erythroleukaemia: the p53 locus. Cancer Surv. 12:137-151.
45. Jonasson, J., S. Povey, and H. Harris. 1977. The analysis of malignancy by cell fusion. VII. Cytogenetic analysis of hybrids between malignant and diploid cells and of tumours derived from them. J. Cell Sci. 24:217-254.
46. Jones, P. A. 1996. DNA methylation errors and cancer. Cancer Res. 56:2463-2467.
47. Kamb, A., N. A. Gruis, J. Weaver-Feldhaus, Q. Liu, K. Harshman, S. V. Tavtigian, E. Stockert, R. S. Day, B. E. Johnson, and M. H. Skolnick. 1994. A cell cycle regulator potentially involved in genesis of many tumor types. Science 264:436-440.
48. Kinzler, K. W., M. C. Nilbert, L. K. Su, B. Vogelstein, T. M. Bryan, D. B. Levy, K. J. Smith, A. C. Preisinger, P. Hedge, and D. McKechnie. 1991. Identification of FAP locus genes from chromosome 5q21. Science 253:661-665.
49. Knowles, M. A., P. A. Elder, M. Williamson, J. P. Cairns, M. E. Shaw, and M. G. Law. 1994. Allelotype of human bladder cancer. Cancer Res. 54:531-538.
50. Knudson, A. G. 1993. Antioncogenes and human cancer. Proc. Natl. Acad. Sci. USA 90:10914-10921.
51. Kunimi, K., U. S. Bergerheim, I. L. Larsson, P. Ekman, and V. P. Collins. 1991. Allelotyping of human prostatic adenocarcinoma. Genomics 11:530-536.
52. Lane, D. P. 1994. p53 and human cancers. Br. Med. Bull. 50:582-599.
53. Largaespada, D. A., J. D. Shaughnessy, N. A. Jenkins, and N. G. Copeland. 1995. Retroviral integration at the Evi-2 locus in BXH-2 myeloid leukemia cell lines disrupts Nf1 expression without changes in steady-state Ras-GTP levels. J. Virol. 69:5095-5102.
54. Lee, G. H., K. Ogawa, H. Nishimori, and N. R. Drinkwater. 1995. Most liver epithelial cell lines from C3B6F1 mice exhibit parentally-biased loss of heterozygosity at the Lci (Liver cell immortalization) locus on chromosome 4. Oncogene 11:2281-2287.
55. Li, Q. X., and H. Fan. 1990. Combined infection by Moloney murine leukemia virus and a mink cell focus-forming virus recombinant induces cytopathic effects in fibroblasts or in long-term bone marrow cultures from preleukemic mice. J. Virol. 64:3701-3711.
56. Lindblom, A., L. Skoog, S. Rotstein, B. Werelius, C. Larsson, and M. Nordenskjold. 1993. Loss of heterozygosity in familial breast carcinomas. Cancer Res. 53:4356-4361.
57. Manenti, G., L. De Gregorio, M. Gariboldi, T. A. Dragani, and M. A. Pierotti. 1995. Analysis of loss of heterozygosity in murine hepatocellular tumors. Mol. Carcinog. 13:191-200.
58. Merlo, A., E. Gabrielson, F. Askin, and D. Sidransky. 1994. Frequent loss of chromosome 9 in human primary non-small cell lung cancer. Cancer Res. 54:640-642.
59. Merlo, A., E. Gabrielson, M. Mabry, R. Vollmer, S. B. Baylin, and D. Sidransky. 1994. Homozygous deletion on chromosome 9p and loss of heterozygosity on 9q, 6p, and 6q in primary human small cell lung cancer. Cancer Res. 54:2322-2326.
60. Mowat, M., A. Cheng, N. Kimura, A. Bernstein, and S. Benchimol. 1985. Rearrangements of the cellular p53 gene in erythroleukaemic cells transformed by Friend virus. Nature 314:633-636.
61. Mulligan, L. M., E. Gardner, B. A. Smith, C. G. Mathew, and B. A. Ponder. 1993. Genetic events in tumour initiation and progression in multiple endocrine neoplasia type 2. Genes Chromosomes Cancer 6:166-177.
62. Niwa, O., and R. Kominami. 1992. Lack of allelic preference in amplification and loss of the c-myc oncogene in methylcholanthrene-induced mouse sarcomas. Jpn. J. Cancer Res. 83:1192-1197.
63. Nobori, T., K. Miura, D. J. Wu, A. Lois, K. Takabayashi, and D. A. Carson. 1994. Deletions of the cyclin-dependent kinase-4 inhibitor gene in multiple human cancers. Nature 368:753-756.
64. Ogawa, S., N. Hirano, N. Sato, T. Takahashi, A. Hangaishi, K. Tanaka, M. Kurokawa, T. Tanaka, K. Mitani, and Y. Yazaki. 1994. Homozygous loss of the cyclin-dependent kinase 4-inhibitor (p16) gene in human leukemias. Blood 84:2431-2435.
65. Olopade, O. I., D. L. Buchhagen, K. Malik, J. Sherman, T. Nobori, S. Bader, M. M. Nau, A. F. Gazdar, J. D. Minna, and M. O. Diaz. 1993. Homozygous loss of the interferon genes defines the critical region on 9p that is deleted in lung cancers. Cancer Res. 53:2410-2415.
66. Olopade, O. I., R. B. Jenkins, D. T. Ransom, K. Malik, H. Pomykala, T. Nobori, J. M. Cowan, J. D. Rowley, and M. O. Diaz. 1992. Molecular analysis of deletions of the short arm of chromosome 9 in human gliomas. Cancer Res. 52:2523-2529.
67. Otsuki, T., H. M. Clark, A. Wellmann, E. S. Jaffe, and M. Raffeld. 1995. Involvement of CDKN2 (p16INK4A/MTS1) and p15INK4B/MTS2 in human leukemias and lymphomas. Cancer Res. 55:1436-1440.
68. Quelle, D. E., R. A. Ashmun, G. J. Hannon, P. A. Rehberger, D. Trono, K. H. Richter, C. Walker, D. Beach, C. J. Sherr, and M. Serrano. 1995. Cloning and characterization of murine p16INK4a and p15INK4b genes. Oncogene 11:635-645.
69. Rowe, W. P., W. E. Pugh, and J. W. Hartley. 1970. Plaque assay techniques for murine leukemia viruses. Virology 42:1136-1139.
70. Sato, T., H. Saito, R. Morita, S. Koi, J. H. Lee, and Y. Nakamura. 1991. Allelotype of human ovarian cancer. Cancer Res. 51:5118-5122.
71. Seizinger, B. R., H. P. Klinger, C. Junien, Y. Kakamura, M. Le Beau, W. Cavenee, B. Emanuel, B. Ponder, S. Naylor, F. Mitelman, D. Louis, A. Menon, I. Newsham, J. Decker, M. Kaelbling, I. Henry, and A. V. Deimling. 1991. Report of the committee on chromosome and gene loss in human neoplasia. Cytogenet. Cell Genet. 58:1080-1096.
72. Selten, G., H. T. Cuypers, M. Zijlstra, C. Melief, and A. Berns. 1984. Involvement of c-myc in MuLV-induced T cell lymphomas in mice: frequency and mechanisms of activation. EMBO J. 3:3215-3222.
73. Seymour, A. B., R. H. Hruban, M. Redston, C. Caldas, S. M. Powell, K. W. Kinzler, C. J. Yeo, and S. E. Kern. 1994. Allelotype of pancreatic adenocarcinoma. Cancer Res. 54:2761-2764.
74. Soussi, T., Y. Legros, R. Lubin, K. Ory, and B. Schlichtholz. 1994. Multi-factorial analysis of p53 alteration in human cancer: a review. Int. J. Cancer 57:1-9.
75. Steffen, D. 1984. Proviruses are adjacent to c-myc in some murine leukemia virus-induced lymphomas. Proc. Natl. Acad. Sci. USA 81:2097-2101.
76. Stoler, A., and N. Bouck. 1985. Identification of a single chromosome in the normal human genome essential for suppression of hamster cell transformation. Proc. Natl. Acad. Sci. USA 82:570-574.
77. Stoye, J. P., and J. M. Coffin. 1987. The four classes of endogenous murine leukemia virus: structural relationships and potential for recombination. J. Virol. 61:2659-2669.
78. Stoye, J. P., and J. M. Coffin. 1988. Polymorphism of murine endogenous proviruses revealed by using virus class-specific oligonucleotide probes. J. Virol. 62:168-175. (Erratum, 62:2530.)
79. Stoye, J. P., W. N. Frankel, and J. M. Coffin. 1991. DNA hybridization in dried gels with fragmented probes: an improvement over blotting techniques. Technique 3:123-128.
80. Stoye, J. P., C. Moroni, and J. M. Coffin. 1991. Virological events leading to spontaneous AKR thymomas. J. Virol. 65:1273-1285.
81. Strauss, W. M. 1988. Preparation of genomic DNA from mammalian tissue, p. 2.2.1. In F. R. Ausubel, R. Brent, R. E. Kingston, D. D. Moore, J. G. Seidman, J. A. Smith, and K. Struhl (ed.), Current protocols in molecular biology. John Wiley, New York, N.Y.
82. Tabor, S., and K. Struhl. 1988. Labelling of DNA by random oligonucleotide-primed synthesis, p. 3.5.9. In F. R. Ausubel, R. Brent, R. E. Kingston, D. D. Moore, J. G. Seidman, J. A. Smith, and K. Struhl (ed.), Current protocols in molecular biology. John Wiley, New York, N.Y.
83. Takeuchi, S., C. R. Bartram, T. Seriu, C. W. Miller, A. Tobler, J. W. Janssen, A. Reiter, W. D. Ludwig, M. Zimmermann, and J. Schwaller. 1995. Analysis of a family of cyclin-dependent kinase inhibitors: p15/MTS2/INK4B, p16/MTS1/INK4A, and p18 genes in acute lymphoblastic leukemia of childhood. Blood 86:755-760.
84. Takeuchi, S., C. R. Bartram, M. Wada, A. Reiter, Y. Hatta, T. Seriu, E. Lee, C. W. Miller, I. Miyoshi, and H. P. Koeffler. 1995. Allelotype analysis of childhood acute lymphoblastic leukemia. Cancer Res. 55:5377-5382.
85. Teich, N. 1984. Taxonomy of retroviruses, p. 25-207. In R. Weiss, N. Teich, H. Varmus, and J. Coffin (ed.), RNA tumor viruses. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y.
86. Tsichlis, P. N., P. G. Strauss, and M. A. Lohse. 1985. Concerted DNA rearrangements in Moloney murine leukemia virus-induced thymomas: a potential synergistic relationship in oncogenesis. J. Virol. 56:258-267.
87. Tsuchiya, E., Y. Nakamura, S. Y. Weng, K. Nakagawa, S. Tsuchiya, H. Sugano, and T. Kitagawa. 1992. Allelotype of non-small cell lung carcinoma - comparison between loss of heterozygosity in squamous cell carcinoma and adenocarcinoma. Cancer Res. 52:2478-2481.
88. van der Putten, H., W. Quint, J. van Raaij, E. R. Maandag, I. M. Verma, and A. Berns. 1981. M-MuLV-induced leukemogenesis: integration and structure of recombinant proviruses in tumors. Cell 24:729-739.
89. van der Riet, P., H. Nawroz, R. H. Hruban, R. Corio, K. Tokino, W. Koch, and D. Sidransky. 1994. Frequent loss of chromosome 9p21-22 early in head and neck cancer progression. Cancer Res. 54:1156-1158.
90. Vogelstein, B., E. R. Fearon, S. E. Kern, S. R. Hamilton, A. C. Preisinger, Y. Nakamura, and R. White. 1989. Allelotype of colorectal carcinomas. Science 244:207-211.
91. Wallace, R. B., and Miyada. 1987. Hybridization to DNA in dried agarose gels (unblots). Methods Enzymol. 152:440-442.
92. Weinberg, R. A. 1991. Tumor suppressor genes. Science 254:1138-1146.
93. Wiener, F., S. Ohno, J. Spira, N. Haran-Ghera, and G. Klein. 1978. Chromosome changes (trisomies #15 and 17) associated with tumor progression in leukemias induced by radiation leukemia virus. J. Natl. Cancer Inst. 61: 227-237.
94. Wiseman, R. W. 1995. Personal communication.
95. Yamaguchi, T., J. Toguchida, T. Yamamuro, Y. Kotoura, N. Takada, N. Kawaguchi, Y. Kaneko, Y. Nakamura, M. S. Sasaki, and K. Ishizaki. 1992. Allelotype analysis in osteosarcomas: frequent allele loss on 3q, 13q, 17p, and 18q. Cancer Res. 52:2419-2423.
96. Zhuang, S., L. K. Eklund, C. Cochran, G. N. Rao, R. W. Wiseman, and P. Soderkvist. 1996. Allelotype analysis of 2′,3′-dideoxycytidine- and 1,3-butadiene-induced lymphomas in B6C3F1 mice. Cancer Res. 46:3338-3343.