Factors to consider in the use of stem cells for pharmaceutic drug development and for chemical safety assessment

Toxicology

Volumn 270, Issue 1, 2010, Pages 18-34

  Trosko, James Edward ^a   Chang, Chia Cheng ^a  

^a MICHIGAN STATE UNIVERSITY   (United States)

Author keywords

Adult human stem cells; Barker hypothesis; Epigenetic toxicology; Gap junctions; Side population cells

Indexed keywords

2,3,7,8 TETRACHLORODIBENZO PARA DIOXIN; ACETYLSALICYLIC ACID; BOVINE SERUM ALBUMIN; DIETHYLSTILBESTROL; ESTRADIOL; FUNGICIDE; GENISTEIN; SOYBEAN PROTEIN; VALPROIC ACID; VINCLOZOLIN;

ADULT STEM CELL; ANIMAL TESTING ALTERNATIVE; ARTICLE; CANCER RESISTANCE; CELL DIFFERENTIATION; CELL INTERACTION; CYTOTOXICITY; DRUG SAFETY; DRUG SCREENING; DRUG SENSITIVITY; EMBRYONIC STEM CELL; GENE EXPRESSION REGULATION; GENETIC EPIGENESIS; GENOTOXICITY; HUMAN; IONIZING RADIATION; MALIGNANT TRANSFORMATION; MESENCHYMAL STEM CELL; MULTIPLE CHEMICAL SENSITIVITY; MUTAGENESIS; NONHUMAN; NUCLEAR REPROGRAMMING; PLURIPOTENT STEM CELL; PRENATAL EXPOSURE; PRIORITY JOURNAL; STEM CELL; TERATOGENESIS; TOXICITY TESTING;

ANIMALS; CELL SURVIVAL; DRUG DISCOVERY; DRUG INDUSTRY; EMBRYONIC STEM CELLS; EPIGENESIS, GENETIC; FEMALE; HUMANS; MUTAGENICITY TESTS; NUCLEAR REPROGRAMMING; PHARMACEUTICAL PREPARATIONS; PREGNANCY; SAFETY; STEM CELLS; TOXICOLOGY;

ANIMALIA; RODENTIA;

EID: 77950023356     PISSN: 0300483X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.tox.2009.11.019     Document Type: Article

References (211)

1. Ahn E.H., Chang C.C., Schroeder J.J. Evaluation of sphinganine and sphingosine as human breast cancer chemotherapeutic and chemopreventive agents. Exp. Biol. Med. 2006, 231:1664-1672.
2. Al Hajj M., Wicha M.S., Benito-Hernandez A., Morrison S.J., Clarke M. Prospective identification of tumorigenic breast cancer cells. Proc. Natl. Acad. Sci. U.S.A. 2003, 100:3983-3988.
3. Ames B.N., Durston W.E., Yamasaki E., Lee F.D. Carcinogens as mutagens: a simple test system combining homogenates for activation and bacteria for detection. Proc. Natl. Acad. Sci. U.S.A. 1973, 70:2281-2285.
4. Anderson M.E., Clewell H.J., Bermudez E., Willson G.A., Thomas R.S. Genomic signatures and dose-dependent transitions in nasal epithelial responses to inhaled formaldehyde in the rat. Toxicol. Sci. 2008, 105:368-383.
5. Anway M.D., Cupp A.S., Uzumcu M., Skinner M.K. Epigenetic transgenerational actions of endocrine disruptors and male fertility. Science 2005, 308:1466-1469.
6. Aoi T., Yae K., Nakagawa M., Iscisdaka T., Okita K., Takahashi K., Chiba T., Yamanaka S. Generation of pluripotent stem cells from adult mouse liver and stomach cells. Science 2008, 321:699-702.
7. Atlasi Y., Mowla S.J., Ziaee S.A., Bahrami A.R. OCT-4, an embryonic stem cell marker, is highly expressed in bladder cancer. Int. J. Cancer 2007, 120:1598-1602.
8. Azuma M., Hirao A., Takubo K., Hamaguchi I., Kitamura T., Suda T. A quantitative matrigel assay for assessing repopulation capacity of prostate stem cells. Biochem. Biophys. Res. Commun. 2005, 338:1164-11790.
9. Barcellos-Hoff M.H., Park C., Wright E.G. Radiation and the microenvironment: tumorigenesis and therapy. Nat. Rev. Cancer 2005, 5:867-875.
10. Barker D.J. The developmental origins of adult disease. J. Am. Coll. Nutr. 2004, 236:588s-595s.
11. Beaupain R., Prévost G., Mainguené C., Lainé-Bidron C., Tamboise A., Tamboise E. Continous three-dimensional cultures of MCF-7 cells in serum free medium. In Vitro Dev. Biol. 1993, 29:893-898.
12. Behbod F., Xian W., Shaw C.A., Hilsenbeck S.G., Tsimelzon A., Rosen J.M. Transcriptional profiling of mammary gland side population cells. Stem Cells 2006, 24:1065-1074.
13. Brash D.E., Rudolph J.A., Simon J.A., Lin A., McKenna G.J., et al. A role for sunlight in skin cancer: UV-induced p53 mutations in squamous cell carcinomas. Proc. Natl. Acad. Sci. U.S.A. 1991, 88:10124-10128.
14. Braydich-Stolle L., Hussain S., Schlager J.J., Hofmann M.C. In vitro cytotoxicity of nanoparticles in mammalian germline stem cell. Toxicol. Sci. 2005, 88:412-419.
15. Brody H. A system view of man: implications for medicine, science and ethics. Perspect. Biol. Med. 1973, 17:71-92.
16. Bug G., Gul H., Schwarz K., Pfeifer H., Kampfmann M., Zheng X., Beissert T., Boehrer S., Hoelzer D., Ottmann O.G., Ruthardt M. Valproic acid stimulates proliferation and self-renewal of hematopoietic stem cells. Cancer Res. 2005, 65:2537-2541.
17. Butcher E.C. Can cell systems biology rescue drug discovery?. Nat. Rev./Drug Discov. 2005, 4:461-467.
18. Calabrese E.J. Hormesis: why it is important to toxicology and toxicologists. Environ. Toxicol. Chem. 2008, 27:1451-1474.
19. Cezar G.G., Quam J.A., Smith A.M., Rosa G.J.M., Piekarczyk M.S., Brown J.E., Gage F.H., Muotri A.R. Identification of small molecules from human embryonic stem cells using metabolomics. Stem Cells Dev. 2007, 16:1-14.
20. Challen G.A., Little M.H. A side order of stem cells: the SP phenotype. Stem Cells 2006, 24:3-12.
21. Chang C.C., Sun W., Cruz A., Saitoh M., Tai M.H., Trosko J.E. A human breast epithelial cell type with stem cell characteristics as target cells for carcinogenesis. Radiat. Res. 2001, 155:201-207.
22. Chepko G., Dickson R.B. Ultrastructure of the putative stem cell niche in rat mammary epithelium. Tissue Cell 2003, 35:83-93.
23. Chiba T., Kita K., Zheng Y.W., Yokosuka O., Saisho H., Iwama A., Nakauchi H., Taniguchi H. Side population purified from hepatocellular carcinoma cells harbors cancer stem cell-like properties. Hepatology 2006, 44:240-251.
24. Chiou S.H., Yu C.C., Huang C.Y., Lin S.C., Liu C.J., Tsai T.H., Chou S.H., Chien C.S., Ku H.H., Lo J.F. Positive correlations of Oct-4 and Nanog in oral cancer stem-like cells and high-grade oral squamous cell carcinoma. Clin. Cancer Res. 2008, 14:4085-4095.
25. Cho H.H., Park H.T., Kim Y.J., Bae Y.C., Suh K.T., Jung J.S. Induction of osteoblastic differentiation of human mesenchymal stem cells by histone deacetylase inhibitors. J. Cell Biochem. 2005, 15:533-542.
26. Cleaver J.E. Xeroderma pigmentosum: genetic and environmental influences in skin carcinogenesis. J. Dermatol. 1978, 17:435-444.
27. Cohen G.M., Bracken W.H., Iyer R.P., Berry D.L., Selkirk J.K., Slaga T.J. Anticarcinogenic effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin on benzo(a) pyrene and 7,12-dimethylbenz(a) anthracene tumor initiation and its relationship to DNA binding. Cancer Res. 1979, 39:4027-4033.
28. Cohen J., Enserink M. HIV, HPV Researchers Honored, but one scientist is left out. Science 2008, 322:174-175.
29. Coppe J.P., Kauser K., Campisi J., et al. Secretion of vascular endothelial growth factor by primary human fi broblasts at senescence. J. Biol. Chem. 2006, 281:29568-29574.
30. Csete M. Oxygen in the cultivation of stem cells. Ann. N. Y. Acad. Sci. 2005, 1049:1-8.
31. D' Amato R.J., Loughnan M.S., Flynn E., Folkman J. Thalidomide is an inhibitor of angiogenesuis. Proc. Natl. Acad. Sci. U.S.A. 1994, 91:4082-4085.
32. Daston G.P. Gene expression, dose-response, and phenotypic anchoring: applications for toxicogenomics in risk assessment. Toxicol. Sci. 2008, 105:233-234.
33. de-Feijter A.W., Ray J.S., Weghorst C.M., Klaunig J.E., Goodman J.I., Chang C.C., Ruch R.J., Trosko J.E. Infection of rat liver epithelial cells with v-Ha-ras: correlation between oncogene expression, gap junctional communication, and tumorigenicity. Mol. Carcinog. 1990, 3:54-67.
34. De Maziere A.M.G.L., Scheuermann D.W. Increased gap junctional area in rat liver after administration of dibutyryl cAMP. Cell Tissue Res. 1985, 239:651-655.
35. 2+ in the control of electrical coupling in heart fibers. Biochim. Biophys. Acta 1986, 888:91-99.
36. Denath J., Brugge J.S. Modeling glandular epithelial cancers in three dimensional cultures. Nat. Rev. Cancer 2005, 5:675-688.
37. De Witt Hamer P.C., van Tilborg A.A.G., Eijk P.P., Van Noorden C.J.F., Ylstra B., Leenstra S. The genomic profile of human malignant glioma is altered early in primary cell culture and preserved in speroids. Oncogene 2007, 27:2091-2096.
38. DiPaolo J.A. Relative difficulties in transforming human and animal cells in vitro. J. Natl. Cancer Inst. 1983, 70:3-8.
39. Diwan B.A., Rice J.M., Ohshima M., Ward J.M. Comparative tumor-promoting activities of phenobarbital, amobarbital, barbital sodium, and brbituric acid on livers and other organs of male F344/NCr rats following initiation with N-nitrosdiethylamine. J. Natl. Cancer Inst. 1985, 74:509-515.
40. Doliny D.C., Weidman J.R., Waterland R.A., Jirtle R.L. Maternal genistein alters coat color and protects Avy mouse offspring from obesity by modifying the fetal epigenome. Environ. Health Perspect. 2006, 114:567-572.
41. Doyle L.A., Ross D.D. Multidrug resistance mediated by the breast cancer resistance protein BCRP (ABCG2). Oncogene 2003, 22:7340-7358.
42. Emre N., Coleman R., Ding S. A chemical approach to stem cell biology. Curr. Opin. Chem. Biol. 2007, 11:252-258.
43. Enat R., Jefferson D.M., Ruiz-Opazo N., Gatmaitan Z., Leinwand L., Reid L.M. Hepatocyte proliferation in vitro: its dependence on the use of serum-free, hormonally defined medium and substrata of extracellular matrix. Proc. Natl. Acad. Sci. U.S.A. 1984, 81:1411-1415.
44. Fialkow P.J. Clonal origin of human tumours. Ann. Rev. Med. 1979, 30:135-176.
45. Fink D.W. Human embryonic stem cells and the Food and Drug Administration. Human Embryonic Stem Cells 2004, 323-343. Humana Press, Totowa, NJ. A. Chiu, M.S. Rao (Eds.).
46. Fischer S.M., Klein-Szanto J.P., Adams L.M., Slaga T.J. The first stage and complete promoting activity of retinoic acid, but not the analog RO-10-9359. Carcinogenesis 1985, 6:575-578.
47. Fishman M.C., Porter J.A. A new grammer for drug discovery. Nature 2005, 437:491-493.
48. Forbes P.D., Urbach F., Davies R.E. Enhancement of experimental photocarcinogenesis by topic retinoic acid. Cancer Lett. 1979, 7:85-90.
49. French A.J., Adams C.A., Anderson L.S., Kitchen J.R., Hughes M.R., Wood S.H. Development of human cloned blastocysts following somatic cell nuclear transfer with adult fibroblasts. Stem Cells 2008, 26:485-493.
50. Fritsche E., Cline J.E., Nguyen N.H., Scanlan T.S., Abel J. Polychlorinated biphenyls disturb differentiation of normal human neural progenitor cells: clue for involvement of thyroid hormone receptors. Environ. Health Perspect. 2005, 113:871-876.
51. Fuchs E., Tumbar T., Guasch G. Socialing with the neighbors: stem cells and their niche. Cell 2004, 116:769-778.
52. Fukushima S., Kinoshita A., Puutanachokchai R., Kushida M., Wanibuchi H., Morimura K. Hormeisis band dose response-mediated mechanisms in carcinogenesis: evidence for a threshold in carcinogenicity of non-genotoxic carcinogens. Carcinogenesis 2005, 26:1835-1845.
53. Ghosh S., Spagnoli G.C., Martin I., Ploegert S., Demougin P., Heberer M., Reschner A. Three-dimensional culture of melanoma cells profoundly affects gene expression prolife: a high density oligonucleotide array study. J. Cell. Physiol. 2005, 204:522-531.
54. Gladwell S.J., Jefferys J.G.R. Second messenger modulation of electrotonic coupling between region CA3 pyramidal cell axons in the hippocampus. Neurosci. Lett. 2001, 200:1-4.
55. Goldsworthy T., Campbell H.A., Pitot H.C. The natural history and dose-response characteristics of enzyme-altered foci in the rat liver following Phenobarbital and diethylnitroamine administration. Carcinogenesis 1984, 5:67-71.
56. Goodell M.A., Brose K., Paradis G., Conner A.S., Mulligan R.C. Isolation and functional properties of murine hematopoietic stem cells that are replicating in vivo. J. Exp. Med. 1996, 183:1797-1806.
57. Hadnagy A., Gaboury L., Beaulieu R., Balicki D. SP analysis may be used to identify cancer stem cell populations. Exp. Cell Res. 2006, 312:3701-3710.
58. Hammond S.L., Ham R.G., Stampfer M.R. Serum-free growth of human mammary epithelial cells: rapid clonal growth in defined medium and extended serial passage with pituitary extract. Proc. Natl. Acad. Sci. U.S.A. 1984, 81:5435-5439.
59. Haraguchi N., Utsunomiya T., Inoue H., Tanaka F., Mimori K., Barnard G.F., Mori M. Characterization of a side population of cancer cells from human gastrointestinal system. Stem Cells 2006, 24:506-513.
60. Hayashi T., Nomata K., Chang C.C., Ruch R.J., Trosk J.E. Cooperative effects of v-myc and c-Has-ras oncogenes on gap junction intercellular communication and tumorigenicity in rat liver epithelial cells. Cancer Lett. 1998, 128:145-154.
61. Henning H., Wenk M.L., Donahoe R. retinoic acid promotion of papilloma formation in mouse skin. Cancer Lett. 1982, 16:1-5.
62. Herskind C., Rodemann H.P. Spontaneous and radiation-induced differentiation of fibroblasts. Exp. Gerontol. 2000, 35:747-755.
63. Ho M.M., Ng A.V., Lam S., Hung J.Y. Side population in human lung cancer cell lines and tumors is enriched with stem-like cancer cells. Cancer Res. 2007, 67:4827-4833.
64. Hochedlinger K., Yamada Y., Beard C., Jaenisch R. Ectopic expression of Oct-4 blocks progenitor-cell differentiation and caused Dysplasia in epithelial tissues. Cell 2005, 121:465-477.
65. Holsapple M.P., Pitot H.C., Cohen S.H., Boobis A.R., Klaunig J.E., Pastoor T., Dellarco V.L., Dragan Y.P. Mode of action in relevance of rodent liver tumors to human cancer risk. Toxicol. Sci. 2006, 89(1):51-56.
66. Hsieh C.Y., Chang C.C. Stem cell differentiation and reduction as a potential mechanism for chemoprevention of breast cancer. Chin. Pharm. J. 1999, 51:15-30.
67. Hussain S.Z., Strom S.C., Kirby M.R., Burns S., Langemeijer S., Ueda T., Hsieh M., Tisdale J.F. Side population cells derived from adult human liver generate hepatocyte-like cells in vitro. Dig. Dis. Sci. 2005, 50:1755-1763.
68. Iivanainen M., Savolainen H. Side effects of phenobarbital and phenytoin during long term treatment of epilepsy. Acta Neurol. Scand. Suppl. 2007, 97:49-67. 1983.
69. Ince T.A., Richardson A.L., Bell G.W., Saitoh M., Godar S., Karnoub A.E., Iglehart J.D., Weinberg R.A. Transformation of different human breast epithelial cell types leads to distinct tumor phenotype. Cancer Cell 2007, 12:160-170.
70. Inoue M., Yoshimi I., Sobue T., Tsugane S. Influence of coffee drinking on subsequent risk of hepatocellular carcinoma: a prospective study in Japan. J. Natl. Cancer Inst. 2005, 97:293-300.
71. Ito N., Hirose M., Fukushima S., Tsuda T., Tatematsu M. Studies on antioxidants: their carcinogenic and modifying effects on chemical carcinogenesis. Fd. Chem. Toxic. 1986, 24:1071-1082.
72. Kalimi G.H., Sirsat S.M. Phorbol ester tumor promoter affects and mouse epidermal gap junctions. Cancer Lett. 1984, 22:343-350.
73. Kamishina H., Cheeseman J.A., Clemmons R.M. Nestin-positive spheres derived from canine bone marrow stromal cells generate cells with early neuronal and glial phenotypic characteristics. In Vitro Cell Dev. Biol. Anim. 2008, 44:140-144.
74. Kang K.S., Morita I., Cruz A., Jeon Y.J., Trosko J.E., Chang C.C. Expression of estrogen receptors in a normal human breast epithelial cell type with luminal and stem cell characteristics and in neoplastically transformed cell lines. Carcinogenesis 1997, 18:251-257.
75. c-erbB2/neu in tumorigenicity induced by X-rays and the neu oncogene in human breast epithelial cells. Mol. Carcinog. 1998, 21:225-233.
76. Kao C.Y., Oakley C.S., Welsch C.W., Chang C.C. Growth requirements and neoplastic transformation of two types of normal human breast epithelial cells derived from reduction mammaoplasty. In Vitro Cell. Dev. Biol. Anim. 1997, 33:282-288.
77. Kao C.Y., Nomata K., Oakley C.S., Welsch C.W., Chang C.C. Two types of normal human breast epithelial cells derived from reduction mammoplasty: phenotypic characterization and response to SV40 transfection. Carcinogenesis 1995, 16:531-538.
78. Kelley P.N., Dakic A., Adams J.M., Nutt S.L., Strasser A. Tumor growth need not be driven by rare stem cells. Science 2007, 317:337.
79. Kim J.B., Zaehres H., Wu G., Gentile L., Ko K., Sebastiano V., Arauzo-Bravo M.J., Ruau D., Han D.W., Zenke M., Scholer H.R. Pluripotent stem cells induced from adult neural stem cells by reprogramming with two factors. Nature 2008, 454:646-651.
80. Kim M., Turnquist H., Jackson J., Sgagias M., Yan Y., Gong M., Dean M., Sharp J.G., Cowan K. The multidrug resistance transporter ABCG2 (breast cancer resistance protein 1) effluxes Hoechst 33342 and is overexpressed in hematopoietic stem cells. Clin. Cancer Res. 2002, 8:22-28.
81. Kim S.J., Lee B.H., Lee Y.S., Kang K.S. Defective cholesterol traffic and neuronal differentiation in neural stem cells of Niemann-Pick type C disease improved by valproic acid, a histone deacetylase inhibitor. Biochem. Biophys. Res. Commun. 2007, 360:593-599.
82. King T.J., Fukushima L.H., Donlon T.A., et al. Correlation between growth control, neoplastic potential and endogenous connexin43 expression in HeLa cell lines: implications tumor progression. Carcinogenesis 2000, 21:311-315.
83. Klaunig J.E., Ruch R.J. Strain and species effects on the inhibition of hepatocyte intercellular communication by liver tumor promoters. Cancer Lett. 1987, 36:161-168.
84. Kolaja K.L., Stevenson D.E., Walborg E.F., Klanig J.E. Dose dependence of phenobarbital promotion of premalignant hepatic lesions in F344 rats and B6C3F1 mice: effects on DNA synthesis and apoptosis. Carcinogenesis 1996, 17:947-954.
85. Korff T., Krauss T., Augustin H.G. Three-dimensional spheroid culture of cytophoblast cells mimics the phenotype and differentiation of cytorophoblasts from normal and preclamptic pregnancies. Exp. Cell Res. 2004, 292:415-422.
86. Krtolica A., Parrinello S., Lockett S., et al. Senescent fi broblasts promote epithelial cell growth and tumorigenesis: a link between cancer and aging. Proc. Natl. Acad. Sci. U.S.A. 2001, 98:12072-12077.
87. Kubota H., Avarbock M.R., Brinster R. Growth factors essential for self-renewal and expansion of mouse spermatogonial stem cells. Proc. Natl. Acad. Sci. U.S.A. 2004, 101:16489-16494.
88. Kuroki T., Huh N.H. Why are human cells resistant to malignant cell transformation in vitro?. Jpn. J. Cancer Res. 1993, 84:1091-1100.
89. Land H., Parada L.F., Weinberg R.A. Tumorigenic conversion of primary embryo fibroblasts requires at least two cooperating oncogenes. Nature 1983, 304:596-602.
90. Larderet G., Fortunel N.O., Vaigot P., Cegalerba M., Maltere P., Zobiri O., Gidrol X., Waksman G., Martin M.T. Human side population keratinocytes exhibit long-term proliferative potential and a specific gene expression profile and can form a pluristratified epidermis. Stem Cells 2006, 24:965-974.
91. Ledford H. Disputed definitions. Nature 2008, 455:1027.
92. Lee B.M., Park K.K. Beneficial and adverse effects of chemopreventive agents. Mutat. Res. 2003, 523-524:265-278.
93. Lee G.H. Review article: paradoxical effects of phenobarbital on mouse hepatocarcinogenesis. Toxicol. Pathol. 2000, 28:215-225.
94. Lewis J.C., Cheng D., Jordan V.C. Targeting oestrogen to kill the cancer but not the patients. Br. J. Cancer 2004, 90:822-832.
95. Liadaki K., Kho A.T., Sanoudou D., Schienda J., Flint A., Beggs A.H., Kohane I.S., Kunkel L.M. Side population cells isolated from different tissues share transcriptome signatures and express tissue-specific markers. Exp. Cell Res. 2005, 303:360-374.
96. Liao J., Wu Z., Wang Y., Cheng L., Cui C., Gao Y., Chen T., Rao L., Chen S., Jia N., Dai H., Xin S., Kang J., Pei G., Xiao L. Enhanced efficiency of generating induced pluripotent stem (iPS) cells from human somatic cells by a combination of six transcription factors. Cell Res. 2008, 18:800-803.
97. Lin T.M., Tsai J.L., Lin S.D., Lai C.S., Chang C.C. Accelerated growth and prolonged lifespan of adipose tissue-derived human mesenchymal stem cells in a medium using reduced calcium and antioxidants. Stem Cells Dev. 2005, 14:92-102.
98. Linning K.D., Tai M.H., Madhukar B.V., Chang C.C., Reed D.N., Ferber S., Trosko J.E., Olson L.K. Redox-mediated enrichment of self-renewing adult human pancreatic cells which possess endocrine differentiation potential. Pancreas 2004, 29:e64-e76.
99. Liu H., Roy K. Biomimetic three dimensional cultures significantly increases hematopoietic differentiation efficacy of embryonic stem cells. Tissue Eng. 2005, 11:319-330.
100. Liu S.V. iPS cells: SA more critical review. Stem Cells Dev. 2008, 17:391-397.
101. Liu S.V. Are iPS cells really induced from differentiated cells?. Logical Biol. 2008, 81-87.
102. Liu S.V. One factor dropped from the 'inducing soup', one piece of evidence added against the induction claim. Logical Biol. 2008, 8:39-41.
103. Maden M. Vitamin A and pattern formation in the regenerating limb. Nature 1982, 295:672-675.
104. Maekawa A., Onodera H., Ogasawara H., Matsushima Y., Mitsumori K., Hayashi Y. Threshold dose dependence in phenobarbital promotion of rat hepatocarcinogenesis initiated by diethylnitrosamine. Carcinogenesis 1992, 13:501-503.
105. Maher V.M., Ouellette L.M., Curren R.D., McCormick J.J. The frequency of ultraviolet light-induced mutations is higher in xeroderma pigmentosum variants than in normal human cells. Nature 1976, 261:593-595.
106. Majka S.M., Beutz M.A., Hagen M., Izzo A.A., Voelkel N., Helm K.M. Identification of novel resident pulmonary stem cells: form and function of the lung side population. Stem Cells 2005, 23:1073-1081.
107. Manson J.M. Teratogenicity. Cassarett and Doull's Toxicology: The Basic Science of Poisons 1986, MacMillan Publishing Co., New York, pp. 195-220. Third Edition.
108. Morroni M., Giordano A., Zingaretti M.C., Boiani R., De Matteis R., Kahn B.B., Nisolis E., Tonellos C., Pisoschi C., Luchetti M.M., Marelli M., Saverio Cinti S. Reversible transdifferentiation of secretory epithelial cells into adipocytes in the mammary gland. Proc. Natl. Acad. Sci. U.S.A. 2004, 101:16801-16806.
109. Markert C. Genetic control of cell interactions in chimeras. Dev. Genet. 1984, 4:267-279.
110. Martin C.M., Meeson A.P., Robertson S.M., Hawke T.J., Richardson J.A., Bates S., Goetsch S.C., Gallardo T.D., Garry D.J. Persistent expression of the ATP-binding cassette transporter, ABCG-2, identifies cardiac SP cells in the developing and adult heart. Dev. Biol. 2004, 265:262-275.
111. Matsui W., Wang Q., Barber J.P, Brennan S., Smith B.D., Borrello I., McNiece I., Lin L., Ambinder R.F., Peacock C., Watkins D.N., Huff C.A., Jones R.J. Clonogenic multiple myeloma progenitors, stem cell properties, and drug resistance. Cancer Res. 2008, 68:190-197.
112. Mehta P.P., Bertram J.S., Loewenstein W.R. Growth inhibition of transformed cells correlates with their junctional communication with normal cells. Cell 1986, 44:187-196.
113. Minsk B., Illmensi K. Totipotency and normal differentiation of single teratocarcinoma cells cloned by injecting into blastocysts. Proc. Natl. Acad. Sci. U.S.A. 1976, 73:549-553.
114. Moggs J.G., Murphy T.C., Lim F.L., Moore D.J., Stuckey R., Antrobus K., Kimber I., Orphanides G. Anti-proliferative effect of estrogen in breast cancer cells that re-express ER alpha is mediated by aberrant regulation of cell cycle genes. J. Mol. Endocrinol. 2005, 34:535-551.
115. Momiyama M., Omori Y., Ishizaka Y., et al. Connexin26-mediated gap junctional communication reverses the malignant phenotype of MCF-7 breast cancer cells. Cancer Sci. 2003, 94:501-507.
116. Na H.K., Wilson M.R., Kang K.S., Chang C.C., Grunberger D., Trosko J.E. Restoration of gap junctional intercellular communication by caffeic acid phenethyl ester (CAPE) in a ras-transformed rat liver epithelial cell line" Cancer Lett. 2000, 157:31-38.
117. Nakano S., Ueo H., Bruce S.A., Ts'o P.O.P. A contact-insensitive subpopulation in Syrian hamster cell cultures with a greater susceptibility to chemically induced neoplastic transformation. Proc. Natl. Acad. Sci. U.S.A. 1985, 82:5005-5009.
118. National Research Council (2007). Toxicity Testing in the 21st Century: A Vision and a Strategy. National Research Council Committee on Toxicity Testing and Assessment of Environmental Agents, 196pp. Washington, D.C., USA: The National Academies Press. Available at: (Accessed 15.10.08). http://www.nap.edu/catalog.phd?record_id=11970.
119. Nelson C.M., VanDuijn M.M., Inman J.I., Fletcher D.A., Bissell M.J. Tissue geometry determines sites of mammary branching morphogenesis in organotypic cultures. Science 2006, 314:298-301.
120. Neupane M., Chang C.C., Kiupel M., Yuzbasiyan-Gurkan V. Optimization of growth and differentiation of canine adipose-derived mesenchymal stem cells. Tissue Eng. 2008, 14:1007-1015.
121. Neupane, M., Claycombe, K., Chang, C.C., Yuzbasiyan-Gurkan, 2009. Comparison of proliferation and differentiation of adipose-derived mesenchymal stem cells from different mammalian species. In: 8th Annual Pediatric Res. Day Conference, Michigan State University, Detroit, MI.
122. Newbold R.R., Hanson R.B., Jefferson W.N., et al. Increased tumors, but uncompromised fertility in female descendants of mice exposed developmentally to DES. Carcinogenesis 1998, 19:1655-1663.
123. Nicolai S., Sies H., Stahl W. Stimulation of gap junctional intercellular communication by thalidomide and thalidomide analogs in human skin fibroblasts. Biochem. Pharmacol. 1997, 53:1553-1557.
124. Nielson M., Ruch R.J., Vang O. Resveratrol reverses tumor-promoter-induced inhibition of gap junctional intercellular communication. Biochem. Biophys. Res. Commun. 2000, 275:804-809.
125. Nishikawa S.I., Martin L., Era T. Embryonic stem cell culture as a tool for developmental cell biology. Nature 2007, 8:502-507.
126. Nowell P.C. The clonal evolution of tumor cell populations. Science 1976, 194:23-28.
127. Oatley J.M., Avarbock M.R., Telaranta A.I., Fearon D.T., Brinster R.L. Identifying genes important for spermatogonial stem cell self-renewal and survival. Proc. Natl. Acad. Sci. U.S.A. 2006, 103:9524-9529.
128. Okano J., Nagahara T., Matsumoto K., Murawaki Y. Caffeine inhibits the proliferation of liver cancer cells and activates the MEK/ERK/EGFR signalling pathway. Basic Clin. Pharmacol. Toxicol. 2008, 102:543-551.
129. Okita K., Ichisaka T., Yamanaka S. Generation of germline-competent induced pluripotent stem cells. Nature 2007, 448:313-317.
130. Okita K., Nakagawa M., Hyenjong H., Ichisaka T., Yamanaka S. Generation of mouse induced pluripotent stem cells without viral vectors. Science 2008, 322:949-953.
131. Pampaloni F., Reynaud E.C., Stelzer E.K. The third dimension bridges the gap between cell culture and live tissue. Nat. Rev/Mol. Cell Biol. 2007, 8:839-845.
132. Paolini M., Abel-Rahman S.Z., Sapone A., Pedulli G.F., Perocco P., Cantelli-Forti G., Legator M.S. β-Carotene: a cancer chemopreventive agent or a co-carcinogen?. Mutat. Res. 2003, 543:195-200.
133. Papini S., Rosellini A., Nardi M., Giannarini C., Revoltella R.P. Selective growth and exprension of human corneal epithelial basal stem cells in a three-dimensional organ culture. Different 2005, 23:61-68.
134. Park I.H., Zhao R., West J.A., Yabuuchi A., Huo H., Ince T.A., et al. Reprogramming of human somatic cells to pluripotency with defined factors. Nature 2008, 451:141-147.
135. Pearce D.J., Ridler C.M., Simpson C., Bonnet D. Multiparameter analysis of murine bone marrow side population cells. Blood 2004, 103:2541-2546.
136. Pera M. A new year and a new era. Nature 2008, 451:135-136.
137. Pitot H.C., Dragan Y.P. Facts and theories concerning the mechanisms of carcinogenesis. FASEB J. 1991, 5:2280-2286.
138. Pitot H.C., Goldsworthy T.L., Moran S., Kennan W., Glauert H.P., Maronpot R.R., Campbell H.A. A method to quantitate the relative initiating and promoting potencies of hepatocarcinogenic agents in the their dose-response relationships to altered hepatic foci. Carcinogenesis 1987, 8:1491-1499.
139. Pittelkow M.R., Scott R.E. New techniques for the in vitro culture of human skin keratinocytes and perspectives on their use for grafting of patients with extensive burns. Mayo Clin. Proc. 1986, 61:771-777.
140. Potten C.S. Stem cells in gastrointestinal epithelium: numbers. Characteristics and death. Philos. Trans. R. Soc. Lond. [Biol.] 1998, 353(1370):821-830.
141. Potter V.R. The probabilistic aspects of the human cybernetic machine. Perspect. Biol. Med. 1974, 17:71-92.
142. Quintana E., Shackleton M., Sabel M.S., Fullen D.R., Johnson T.M., Morrison S.J. Efficient tumor formation by single human melanoma cells. Nature 2008, 456:593-598.
143. Rae R.S., Mehta P.P., Chang C.C., Trosko J.E., Ruch R.J. Neoplastic phenotype of gap-junctional intercellular communication-deficient WB rat liver epithelial cells and its reversal by forced expression of connexin 32. Mol. Carcinogen. 1998, 22:120-127.
144. Reik W. Stability and flexibility of epigenetic gene regulation in mammalian development. Nature 2007, 447:425-432.
145. Renm P., de Feijter A.W., Paul D.L., Ruch R.J. Enhancement of liver cell gap junction protein expression by glucorticoids. Carcinogenesis 1994, 15:1807-1813.
146. Rhim J.S. Neoplastic transformation of human cells in vitro. Crit. Rev. Oncog. 1993, 4:313-335.
147. Rodriguez A.M., Pisani D., Dechesne C.A., Turc-Carel C., Kurzenne J.V., Wdziekonski B., Villageois A., Bagnis C., Breittmayer J.P., Groux H., Aihaud G., Dani C. JEM 2005, 201:1397-1405.
148. Ruiz A., Buzanska L., Gilliland D., Rauscher H., Sirghi L., Sobanki T., Zychowicz M., Ceriotti L., Bretagnol F., Coecke S., Colpo P., Rossi F. Micro-stamped surfaces for the patterned growth of neural stem cells. Biomaterials 2008, 29:4766-4774.
149. Ruiz, A., Buzanska, L., Ceriotti, L., Bretagnol, F., Coecke, S., Colpo, P., Rossi, F., 2008. Stem-cell culture on patterned bio-functional surfaces. J. Biomater. Sci. Polym. Ed. XXX, 1-9.
150. Sai K., Kanno J., Hasegawa R., Trosko J.E., Inoue T. Prevention of the down-regulation of gap junctional intercellular communication by green tea in the liver of mice fed pentachlorophenol. Carcinogenesis 2000, 21:1671-1676.
151. Santini M.T., Rainaldi G., Indovina P.L. Multicellular tumor spheroid in radiation biology. Int. J. Radiat. Biol. 1999, 75:787-799.
152. Schollnberger H., Mitchel R.J., Redpath J.L., et al. Detrimental and protective effects: a model approach. Radiat. Res. 2007, 168:614-626.
153. Schulte-Hermann R., Grasl-Kraupp B., Bursch W. Dose-response and threshold effects in cytotoxicity and apoptosis. Mutat. Res. 2000, 464:13-18.
154. Shaw K.R.M., Wrobel C.N., Brugge J.S. Use of three dimensional basement membrane culures to model oncogene-induced changes in mammary epithelial morphogenesis. J. Mamm. Gland Biol. Neoplasia 2004, 9:297-310.
155. Shimano K., Satake M., Okaya A., Kitanaka J., Kitanaka N., Takemura M., Sakagami M., Terada N., Tsujimura T. Hepatic oval cells have the side population phenotype defined by expression of ATP-binding cassette transporter ABCG2/BCRP1. Am. J. Pathol. 2003, 163:3-9.
156. Shuin T., Nishimura R., Noda K., Umeda M., Ono T. Concentration-dependent differential effect of retinoic acid on intercellular metabolic cooperation. Gann 1983, 74:100-105.
157. Sinha G. Trying to catch troublemakers with a metabolic profile. Science 2005, 310:965-966.
158. Smalley K.S.M., Lioni M., Herlyn M. Life isn't flat: taking cancer biology to the next dimension. In Vitro Cell Dev. Biol. Anim. 2006, 42:242-247.
159. Song X., Zhu C.H., Xie T., Doan C., et al. Germline stem cells anchored by adherens junctions in the Drosophila ovary niches. Science 2002, 296:1855-1857.
160. Sporn M., Newton D.L. Chemoprevention of cancer by retinoic acid. Fed Proc. 1979, 38:2528-2534.
161. Spradling A., Drummond-Barbosa D., Kai T. Stem cells find their niche. Nature 2001, 414:98-104.
162. Stadtfield M., Nagaya M., Utikal J., Weir G., Hochedlinger K. Induced pluripotent stem cells generated without viral integration. Science 2008, 322:945-949.
163. Stefanidis K., Loutradis D., Vassiliou L.V., Anastasiadou V., Kiapekou E., Nikas V., Patris G., Vlachos G., Rodolakis A., Anatsalis A. Neviraine induces growth arrest and premature senescence in human cervical carcinoma cells. Gynecologic Oncol. 2009.
164. Summer R., Kotton D.N., Sun X., Ma B., Fitzsimmons K., Fine A. Side population cells and Bcrp1 expression in lung. Am. J. Physiol. Lung Cell Mol. Physiol. 2003, 285:L97-L104.
165. Sun W., Kang K.S., Morita I., Trosko J.E., Chang C.C. High susceptibility of a human breast epithelial cell type with stem cell characteristics to telomerase activation and immortalization. Cancer Res. 1999, 59:6118-6123.
166. Szotek P.P., Pieretti-Vanmarcke R., Masiakos P.T., Dinulescu D.M., Connolly D., Foster R., Dombkowski D., Preffer F., MacLaughlin D.T., Donahoe P.K. Ovarian cancer side population defines cells with stem cell-like characteristics and Mullerian Inhibiting Substance responsiveness. Proc. Natl. Acad. Sci. U.S.A. 2006, 103:11154-11159.
167. Takahashi K., Tanabe K., Ohnuki M., Narita M., Ichisaki T., Tomoda K., et al. Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 2007, 131:861-872.
168. Takahashi K., Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 2006, 126:663-676.
169. Thompson C.B. Apoptosis in the pathogenesis and treatment of disease. Science 1995, 267:1456-1462.
170. Thompson D.E., Mabuchi K., Ron E., Soda M., Tokunaga M., Ochikubo S., Sugimoto S., Ikeda T., Terasaki M., Izumi S. Cancer incidence in atomic bomb survivors. Part II: Solid tumors, 1958-1987. Radiat. Res. 1994, 137:S17-S67.
171. Tlsty T.D., Briot A., Gualberto A., Hall I., Hess S., Hixon M., Kuppuswamy D., Romanov S., Sage M., White A. Genomic instability and cancer. Mutat. Res. 1995, 337:1-7.
172. Törnell J., Snaith M. Transgenic systems in drug discovery: from target identification to humanized mice. Drug Discov. Today 2002, 7:461-470.
173. Trosko J.E., Upham B.L. The emperor wears no clothes in the field of carcinogen risk assessment: Ignored concepts in cancer risk assessment. Mutagenesis 2005, 20:81-92.
174. Trosko J.E., Ruch R.J. Gap junctions as therapeutic targets. Curr. Drug Targets 2002, 3:465-482.
175. Trosko J.E. Hierarchical and cybernetic nature of biologic systems and their relevance to homeostatic adaptation to how low level exposures to oxidative stress-inducing agents. Environ. Health Perspect. 1998, 106:331-339.
176. Trosko J.E. Is the concept of 'tumor promotion' a useful paradigm?. Mol. Carcinogen. 2001, 30:131-137.
177. Trosko J.E., Chang C.C., Madhukar B.V., Dupont E. Intercellular communication: a paradigm for the interpretation of the initiation/promotion/progress model of carcinogenesis. Chemical Induction of Cancer: Modulation and Combination Effects 1996, 205-225. Birkhauser, Boston. J.C. Arcos (Ed.).
178. Trosko J.E. Cancer: a stem cell-based disease?. Stem Cells in Health and Disease 2009, Springer Publishers, Amsterdam. K. Zaenker, T. Dittmar (Eds.).
179. Trosko J.E. Human adult stem cells as the target cell for the initiation of carcinogenesis and for the generation of " cancer stem cells" Intl. J. Stem Cells 2008, 1:8-26.
180. Trosko J.E., Chang C.C., Upham B.L. Modulation of gap junctional communication by 'epigenetic' toxicants: a shared mechanism in teratogenesis, carcinogenesis, atherogenesis, immunomodulation, reproductive- and neuro-toxicities. Biomarkers of Environmentally Associated Disease 2002, 445-454. Lewis Publishers, Boca Raton, FL. S.H. Wilson, W.A. Suk (Eds.).
181. Trosko J.E., Ruch R.J. Cell-cell communication in carcinogenesis. Front. Biosci. 1998, 3:208-236.
182. Trosko, J.E., Tai, M.H., 2006. Adult stem cell theory of the multistage, Multimechanism theory of carcinogenesis: role of inflammation on the promotion of initiated stem cells. In: Dittmar, T. (Ed.), Infection and Inflammation: Impacts on Oncogenesis. S. Karger AG, Amsterdam, pp. 45-65.
183. Trosko J.E. The role of stem cells and gap junctional communication in carcinogenesis. J. Biochem. Mol. Biol. 2003, 36:43-48.
184. Trosko, J.E., Chang, C.C., 1988. Nongenotoxic mechanism in carcinogenesis: role of inhibited intercellular communication. In: Banbury Report 31: Carcinogen Risk Assessment: New Directions in the Qualitative and Quantitative Aspects. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY, pp. 139-170.
185. Trosko J.E. Stem cells and cell-cell communication in the understanding of the role of diet and nutrients in human diseases. J. Food Hygiene Safety 2007, 22:1-14.
186. Trosko J.E., Chang C.C., Wilson M.R., Upham B., Hayashi T., Wade M. Gap junctions and the regulation of cellular functions of stem cells during development and differentiation. Methods 2000, 20:245-264.
187. Trosko J.E. Commentary: " re-programming or selecting adult stem cells?" Stem Cell Rev. 2008, 4:81-88.
188. Tsuda H., Fukushima S., Wanibuchi H., Morimura K., Nakae D., Imaida K., Tatematsu M., Hirose M., Wakabayashi K., Moore M.A. Value of GST-P positive preneoplastic hepatic foci in dose-response studies of hepatocarcinogenesis: evidence for practical thresholds with both genotoxic and nongenotoxic carcinogens. A Review of recent work. Toxicol. Pathol. 2003, 31:80-86.
189. Tumbar T., Guasch G., Greco V., Blanpain C., Lowry W.E., Rendl M., Fuchs E. Defining the epithelial stem cell niche in skin. Science 2004, 303:359-363.
190. Upham B.L., Trosko J.E. Carcinogenic tumor promotion, induced oxidative stress signaling, modulated gap junction function and altered gene expression. Antioxidants Redox Signaling 2009, 11:297-308.
191. van der Greef J., McBurney R.N. Rescuing drug discovery: in vivo systems pathology and systems pharmacology. Nat. Rev./Drug Discov. 2005, 4:961-967.
192. Van Duuren B.L., Sivak A., Segal A., Seidman I., Katz C. Dose-response studies with a pure tumor promoting agent, phorbol myristate acetate. Cancer Res. 1973, 33:2166-2172.
193. Verma P., Verma V., Ray P. Formation and characterization of three dimensional human hepatocyte cell line spheroids on chitosan matrix for in vitro tissue engineering applications. In Vitro Cell Dev. Biol. Anim. 2007, 43:328-337.
194. Vogel G. Human embryonic stem cells may be toxicology's new best friend. Science 2005, 308:1538.
195. Walker B.E. Experimental teratology complications of pregnancy in mice exposed prenatally to DES. Teratology 1983, 27:1-133.
196. Webster J.D., Yuzbasiyan-Gurkan V., Trosko J.E., Chang C.C., Kiupel M. Expression of the embryonic transcription factor Oct4 in canine neoplasms: a potential marker for stem cell subpopulations in neoplasia. Vet. Pathol. 2007, 44:893-900.
197. Weinstein I.B., Cattoni-Celli S., Kirschmeier P., et al. Multistage carcinogenesis involve multiple genes and multiple mechanisms. J. Cell Physiol. 1984, 3:127-137.
198. Weinstein I.B. Mitogenesis is only one factor in carcinogenesis. Science 1991, 251:387-388.
199. Welter J.F., Solchaga L.A., Penick K.J. Simplification of aggregate culture of human mesenchymal stem cells as a chondrogenic screening assay. Biotechniques 2007, 42:732-737.
200. Welsch C.W., Goodrich-Smith M., Brown C.K., Crowe N. Enhancement by retinyl acetate of hormone-induced mammary tumorigenesis in female GR/A mice. J. Natl. Cancer Inst. 1981, 67:935-938.
201. Wernig M., Meissner A., Foreman R., Brambrink T., Ku M., Hochedlinger K., et al. In vitro reprogramming of fibroblasts into a pluripotent ES-cell-like state. Nature 2007, 448:318-326.
202. Williams G.M. Modulation of chemical carcinogenesis by xenobiotics. Fund. Appl. Toxicol. 1984, 4:325-344.
203. William M., Grady W.M., Carethers J.M. Genomic and epigenetic instability in colorectal cancer pathogenesis. Gasteroenterology 2008, 135:1079-1099.
204. Wilson M.R., Close T.W., Trosko J.E. Cell population dynamics (apoptosis, mitosis, and cell-cell communication) during disruption of " homeostasis" Exp. Cell Res. 2000, 254:257-268.
205. Yamada K., Cuklerman M. Modeling tissue morphogenesis and cancer in 3D. Cell 2007, 130:601-610.
206. Yano S., Ito Y., Fujimoto M., Hamazaki T.S., Tamaki K., Okochi H. Characterization and localization of side population cells in mouse skin. Stem Cells 2005, 23:834-841.
207. Yotti L.P., Chang C.C., Trosko J.E. Elimination of metabolic cooperation in Chinese hamster cells by a tumor promoter. Science 1979, 206:1089-1091.
208. Yu J., Vodyanik M.A., Smuga-Otto K., Antoslewicz J., Frane J.L., Tian S., et al. Induced pluripotent stem cells lines derived from human somatic cells. Science 2007, 318:1917-1920.
209. Zhang L., Hu J., Hong T.P., Liu Y.N., Wu Y.H., Li L.S. Monoclonal side population progenitors isolated from human fetal pancreas. Biochem. Biophys. Res. Commun. 2005, 333:603-608.
210. Zhou S., Schuetz J.D., Bunting K.D., Colapietro A.M., Sampath J., Morris J.J., Lagutina I., Grosveld G.C., Osawa M., Nakauchi H., Sorrentino B.P. The ABC transporter Bcrp1/ABCG2 is expressed in a wide variety of stem cells and is a molecular determinant of the side-population phenotype. Nat. Med. 2001, 7:1028-1034.
211. Zhou J., Wulfkuhle J., Zhang H., Gu P., Yang Y., Deng J., Margolick J.B., Liotta L.A., Petricoin E., Zhang Y. Activation of the PTEN/mTOR/STAT3 pathway in breast cancer stem-like cells is required for viability and maintenance. Proc. Natl. Acad. Sci. U.S.A. 2007, 104:16158-16163.