In vivo transgenic bioassays and assessment of the carcinogenic potential of pharmaceuticals

Environmental Health Perspectives

Volumn 106, Issue SUPPL. 1, 1998, Pages 71-80

  Contrera, Joseph F ^a,b   DeGeorge, Joseph J ^b  

^a Office of Testing and Research   (United States)

^b CENTER FOR DRUG EVALUATION AND RESEARCH   (United States)

Author keywords

Animal models; Bioassay; Carcinogenicity; ICH; Pharmaceuticals; Testing guidance; Transgenic

Indexed keywords

BIOASSAY; CARCINOGEN TESTING; CARCINOGENESIS; DRUG DEVELOPMENT; GENETIC MANIPULATION; MOUSE; NEOPLASM; NONHUMAN; PRIORITY JOURNAL; PROTO ONCOGENE; REVIEW; RISK ASSESSMENT; TRANSGENIC ANIMAL; TRANSGENIC MOUSE; TUMOR SUPPRESSOR GENE;

EID: 0031977883     PISSN: 00916765     EISSN: None     Source Type: Journal    
DOI: 10.1289/ehp.98106s171     Document Type: Review

References (82)

1. Stehelin D, Varmus HE, Bishop JM, Vogt PK. DNA related to the transforming gene(s) of avian sarcoma viruses is present in normal avian DNA. Nature 260:170-173 (1976).
2. Murray MJ, Shilo BZ, Shih C, Cowling D, Hsu HW, Weinberg RA. Three different human tumor cell lines contain different oncogenes. Cell 25:355-361 (1981).
3. Krontiris TG, Cooper GM. Transforming activity of human tumor DNAs. Proc Nat Acad Sci USA 78:1181-1184 (1981).
4. Varmus HE. The molecular genetics of cellular oncogenes. Annu Rev Genet 18:553-612 (1984).
5. Ashby J, Tennant RW. Definitive relationships among chemical structure, carcinogenicity and mutagenicity for 301 chemicals by the U.S. NTP. Mutat Res 257:229-306 (1991).
6. Nakasato F, Sakamoto H, Mori M, Hayashi K, Shimosato Y, Nishi M, Takao S, Nakatani K, Terada M, Sugimura T. Amplification of the c-myc oncogene in human stomach cancers. Jpn J Cancer Res 75:737-742 (1984).
7. Bremner R, Baimain A. Genetic changes in skin tumor progression: correlation between presence of a mutant ras gene and loss of heterozygosity on mouse chromosome 7. Cell 61:407-417 (1990).
8. Vogelstein B. Cancer: a deadly inheritance. Nature 348:681-682 (1990).
9. Fearon ER, Vogelstein B. A genetic model for colorectal tumorigenesis. Cell 61:759-767 (1990).
10. Adams JM, Cory S. Transgenic models of tumor development. Science 254:1161-1167 (1991).
11. Hollstein M, Sidransky D, Vogelstein B, Harris CC. p53 mutations in human cancers. Science 253:49-53 (1991).
12. Sullivan N, Gatehouse D, Tweats D. Mutation, cancer and transgenic models: relevance to the toxicology industry. Mutagenesis 8:167-174 (1993).
13. Cleaver JE, Kraemer KH. Pigmentosum and Cockayne syndrome. In: The Metabolic Basis of Inherited Disease, Vol 3 (Scriver CR, Beaudet AL, Sly WS, and Valle D, eds). New York:McGraw-Hill, 1994;4393-4419.
14. Cordero JC. Transgenic mice as future tools in risk assessment. Risk Anal 9:157-168 (1989).
15. Tennant RW, Spalding J, French JE. Evaluation of transgenic mouse bioassays for identifying carcinogens and noncarcinogens. Mutat Res 365:119-127 (1996).
16. Goldsworthy TL, Recio L, Brown K, Donehower LA, Mirsalis JC, Tennant RW, Purchase IFH. Symposium overview: transgenic animals in toxicology. Fundam Appl Toxicol 22:8-19 (1994).
17. Harris CC. 1995 Deichmann Lecture-p53 tumor suppressor gene: at the crossroads of molecular carcinogenesis, molecular : epidemiology and cancer risk assessment. Toxicol Lett 82/83:1-7 (1995).
18. Contrera JF, Jacobs AC, DeGeorge JJ, Chen CC, Choudary JB, DeFelice AF, Fairweather WR, Farrelly JG, Fitzgerald GG, Goheer AM et al. Carcinogenicity testing and the evaluation of regulatory requirements for pharmaceuticals. Regul Toxicol Pharmacol 25:130-145 (1997).
19. Huff J, Haseman J. Long-term chemical carcinogenesis experiments for identifying potential human cancer hazards: collective database of the National Cancer Institute and National Toxicology Program. Environ Health Perspect 96:23-31 (1991).
20. Huff J, Cirvello J, Haseman J, Bucher J. Chemicals associated with site-specific neoplasia in 1394 long-term carcinogenesis experiments in laboratory rodents. Environ Health Perspect 93:247-270 (1991).
21. Gold LS, Slone TH. Prediction of carcinogenicity from 2 vs. 4 sex-species groups in the carcinogenic potency database. J Toxicol Environ Health 39:147-161 (1993).
22. Gold LS, Bernstein L, Magaw R, Slone TH. Interspecies extrapolation in carcinogenesis: prediction between rats and mice. Environ Health Perspect 81:211-219 (1989).
23. Gold LS, Slone TH, Manley NB, Bernstein L. Target organs in chronic bioassays of 533 chemical carcinogens. Environ Health Perspect 93:233-246 (1991).
24. Gray GM, Li P, Shlyakhter I, Wilson R, An empirical examination of factors influencing prediction of carcinogenic hazard across species. Regul Toxicol Pharmacol 22:283-291 (1995).
25. Tennant RW. Stratification of rodent carcinogen ici ty bioassay results to reflect relative human hazard. Mutat Res 286:111-118 (1993).
26. Lijinsky W, Reuber MD, Blackwell BN. Liver tumors induced in rats by oral administration of the antihistamine methapyrilene hydrochloride. Science 209:817-819 (1980).
27. IARC. IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. Vol 66: Some Pharmaceutical Drugs, Lyon:International Agency for Research on Cancer, 1996.
28. Lai DY, Baetcke KP, Vu VT, Cotruvo JA, Eustis SL. Evaluation of reduced protocols for carcinogenicity testing of chemicals: report of a joint EPA/NIEHS workshop. Regul Toxicol Pharmacol 19:183-201 (1994).
29. Haseman JK, Lockhart A. Correlations between chemically related site-specific carcinogenic effects in long-term studies in rats and mice. Environ Health Perspect 101:50-54 (1993).
30. Freedman DA, Gold LS, Lin TH. Concordance between rats and mice in bioassays for carcinogenesis. Regul Toxicol Pharmacol 23:225-232 (1996).
31. Marselos M, Vainio H. Carcinogenic properties of pharmaceutical agents evaluated in the IARC Monographs programme. Carcinogenesis 12:1751-1766 (1991).
32. Shelby MD, Zeiger E. The genetic toxicity of human carcinogens and its implications. Mutat Res 234:83-115 (1990).
33. Munro IC, Lynch BS, Kittur A, Nestmann ER. Modulators of carcinogenesis. Regul Toxicol Pharmacol 21:60-70 (1995).
34. U.S. FDA, Center for Drug Evaluation and Research. Guidance Documents. Washington:U.S. Food and Drug Administration, 1997. Available from http://www.fila.gov/caer/guifLince
35. Goodman JI. A rational approach to risk assessment requires the use of biological information: an analysis of the National Toxicology Program (NTP), final report of the advisory review by the NTP Board of Scientific Counselors. Regul Toxicol Pharmacol 19:51-59 (1994).
36. IARC. Mechanisms of Carcinogenesis in Risk Identification (Vainio H, Magee PN, McGregor DB, McMichael AJ, eds). IARC Sci Publ No 116, Lyon:International Agency for Research on Cancer, 1992.
37. Contrera JF, Jacobs AC, Prasanna HR, Mehta M, Schmidt WJ, DeGeorge JJ. A systemic exposure-based alternative to the maximum tolerated dose for carcinogenicity studies of human pharmaceuticals. J Am Coll Toxicol 14(1):1-10 (1995).
38. Harris CC. Tumor Suppressor Genes, Multistage Carcinogenesis and Molecular Epidemiology. Lyon:International Agency for Research on Cancer, 1992;67-85, 116.
39. Anderson MW, Reynolds SH, You M, Maronpot RR. Role of proto-oncogene activation in carcinogenesis. Environ Health Perspect 98:13-24 (1992).
40. Maronpot RR, Fox T, Malarkey DE, Goldsworthy TL. Mutations in the ras proto-oncogene: clues to etiology and molecular pathogenesis of mouse liver tumors. Toxicology 101(3):125-56 (1995).
41. Marx J. Gene defect identified in common hereditary colon cancer. Science 262:1645 (1993).
42. Weinberg RA. The molecular basis of oncogenes and tumor suppressor genes. Ann NY Acad Sci 758:331-338 (1995).
43. Cox LS, Lane DP. Tumor suppressors, kinases and clamps: how p53 regulates the cell cycle in response to DNA damage. Bioessays 17:501-508 (1995).
44. Levine AJ. The tumor suppressor genes. Annu Rev Biochem 62:623-651 (1993).
45. Malkin D, Li FP, Strong LC, Fraumeni JFJ, Nelson CE, Kim DH, Kassel J, Gryka MA, Bischoff FZ, Tainsky MA. Germ line p53 mutations in a familial syndrome of breast cancer, sarcomas, and other neoplasms. Science 250:1233-1238 (1990).
46. Shen HM, Ong CN (1996). Mutations of the p53 tumor suppressor gene and ras oncogenes in aflatoxin hepatocarcinogenesis. Mutat Res 366:23-44.
47. Tennant RW, French JE, Spalding JW. Identifying chemical carcinogens and assessing potential risk in short-term bioassays using transgenic mouse models. Environ Health Perspect 103:942-950 (1995).
48. U.S. NTP. Toxicology and Carcinogenesis Studies of Phenolphthalein (CAS No 77-09-8) in F344 Rats and B6C3F1 Mice (Feed Studies). Draft Tech Rpt No 465. Research Triangle Park, NC:U.S. National Toxicology Program, 1995.
49. Dunnick JK, Hardisty JF, Herbert RA, Seely JC, FurediMachacek EM, Foley JF, Lacks GJ, Staslewicz JE, French JE. Phenolphthalein rapidly induces malignant hematopoietic tumors and loss of heterozygosity in p53 wild type ailele in heterozygous p53 deficient mice. Toxicol Pathol (in press).
50. Boschman CR, Stryker S, Reddy JK, Rao MS. Expression of p53 protein in precursor lesions and adenocarcinoma of human pancreas. Am J Pathol 145:1291-1295 (1994).
51. Guerrero L, Pellicer A. Mutational activation of oncogenes in animal model systems of carcinogenesis. Mutat Res 185:293-308 (1987).
52. Bos JL. Ras oncogenes in human cancer: a review. Cancer Res 49:4682-4689 (1989).
53. Lowy DR, Willumsen BM. Function and regulation of ras. Annu Rev Biochem 62:851-891 (1993).
54. Manam S, Srorer RD, Prahalada S, Leander KR, Kraynak AR, Ledwith BJ, van Zwieten MJ, Bradley O, Nichols WW. Activation of the Ha-, Ki-, and N-ras genes in chemically induced liver tumors from CD-1 mice. Cancer Res 52(12):3347-3352 (1992).
55. Saitoh A. Most tumors in transgenic mice with human c-Haras gene contain somatically activated transgenes. Oncogene 5:1195-1200 (1990).
56. Yamamoto S, Mitsumori K, Kodama Y, Matsunuma N, Manabe S, Okamiya H, Suzuki H, Fukuda T, Sakamaki Y, Sunaga M et al. Rapid induction of more malignant tumors by various genotoxic carcinogens in transgenic mice harboring human prototype c-Ha-ras gene than in control nontransgenic mice. Carcinogenesis 17(11):2455-2461 (1996).
57. De Vries A, van Oostrom CTM, Hofhuis FMA, Dortant PM, Berg RJW, de Gruijl FR, Wester PW, van Kreijl CF, Capel PJ A, van Steeg H et al. Increased susceptibility to ultraviolet-B and carcinogens of mice lacking the DNA excision repair gene XPA. Nature 377:169-173 (1995).
58. Kraemer KH, Lee MM, Scotto J. DNA repair protects against cutaneous and internal neoplasia: evidence from xeroderma pigmentosum. Carcinogenesis 5:511-514 (1984).
59. Leder A, Kuo A, Cardiff RD, Sinn D, Leder P. v-Ha-ras transgene abrogates the initiation step in mouse skin tumorigenesis: effects of phorbol esters and retinoic acid. Proc Natl Acad Sci USA 87:9178-9182 (1990).
60. Huff JE. Issues and controversies surrounding qualitative strategies for identifying and forecasting cancer causing agents in the human environment. Pharmacol Toxicol 72(Suppl 1): 12-27 (1993).
61. Goodman G, Wilson R. Predicting the carcinogenicity of chemicals in humans from rodent bioassay data. Environ Health Perspect 94:195-218 (1991).
62. Tomatis L, Aitio A, Wilbourn J, Shuker L, Human carcinogens so far identified. Jpn J Cancer Res 80:795-807 (1989).
63. ICCVAM. Validation and Regulatory Acceptance of Toxicological Test Methods: A Report of the Ad Hoc Interagency Coordinating Committee on the Validation of Alternative Methods. NIH Publ No 97-3981. Research Triangle Park, NC:National Institute of Environmental Health Sciences, 1997.
64. Haseman JK, Winbush JS, O'Donnell MW Jr. Use of dual control groups to estimate false positive rates in laboratory animal carcinogenicity studies. Fundam Appl Toxicol 7:573-584 (1986).
65. Rao G, Haseman J, Grumbein S, Crawford S, Eustis S. Growth, body weight, survival and tumor trends in F344/N rats during an eleven-year period. Toxicol Pathol 18:61-70 (1990).
66. Keenan KP, Smith P, Ballam G, Soper K, Bokelman D. The effect of diet and dietary optimization (caloric restriction) on survival in carcinogenicity studies. In: The Carcinogenicity Debate (McAuslane J, Lumley C, Walker S, eds). Lancaster, UK:Quay Publishing Ltd, 1992;77-102
67. Keenan KP, Soper KA. The effects of ad libitum overfeeding and moderate dietary restriction on Sprague-Dawley rar survival, spontaneous carcinogenesis, chronic disease and the toxicologie response to pharmaceuticals. In: Dietary Restriction (Hart RW, Neumann DA, Robertson RT, eds). Washington, ILSI Press, 1995;99-126.
68. Turturro A, Dufry P, Hart R. Modulation of toxicity by diet and dietary macronutrient restriction. Mutat Res 295:151-164 (1993).
69. Haseman JK. A reexamination of false-positive rates for carcinogenicity studies. Fundam Appl Toxicol 3(4):334-339 (1983).
70. Dunning WF, Curtis MR, Segaloff A. Strain differences in response to estrone and the induction of mammary gland, adrenal, and bladder cancer in rats. Cancer Res 13:147-152 (1953).
71. Drew RT, Boorman GA, Haseman JK, McConnell EE, Busey W, Moore JA. The effect of age and exposure duration on cancer induction by a known carcinogen in rats, mice and hamsters. Toxicol Appl Pharmacol 68:120-130 (1983).
72. Drinkwater NR, Ginsler JJ. Genetic control of hepatocarcinogenesis in C57BL/6J and C3H/HEJ inbred mice. Carcinogenesis 7:1701-1707 (1986).
73. Innes JRM, Ulland BM, Valerio MG, Petrucelli L, Fishbein L, Hart, ER Pallotta AJ, Bates RR, Falk HL, Gart JJ et al. Bioassay of pesticides and industrial chemicals for tumorigenicity in mice: a preliminary note. J Natl Cancer Inst 42:1101-1114 (1969).
74. Dragani TA, Maneti G, Garibaldi M, De Gregorio L, Pierotti MA. Genetics of liver tumor susceptibility in mice. Toxicol Lett 82/83:613-619 (1995).
75. Reuber MD. Varying degrees of susceptibility of inbred strains of rats to N-2-fluorenyldiacetamide hepatic carcinogenesis. Toxicol Appl Pharmacol 37:525-530 (1976).
76. Roebuck BD, Longnecker DS. Species and rat strain variation in pancreatic nodule induction by azaserine. J Natl Cancer Inst 59:1273-1277 (1977).
77. Ward JM, Vlahakis G. Evaluation of hepatocellular neoplasms in mice. J Natl Cancer Inst 61:807-810 (1978).
78. Barrett JC, Wiseman RW. Molecular carcinogenesis in humans and rodents. In: Comparative Molecular Carcinogenesis (KleinSzanto AJP, Anderson MW, Barrett JC, Slaga TJ, eds). New York:Wiley-Liss, 1992;1-30.
79. Tarone RE, Chu KC, Ward JM. Variability in the rates of some common naturally occurring tumors in Fischer 344 rats and (C57BL/6N X C3H/HeN)F1 mice. J Natl Cancer Inst 66:1175-1181 (1981).
80. Everett R. Factors affecting spontaneous tumor incidence rates in mice: a literature review. CRC Crit Rev Toxicol 13:235-251 (1984).
81. Seilkop SK. The effect of body weight on tumor incidence and carcinogenicity testing in B6C3F1 mice and F344 rats. Fundam Appl Toxicol 24:247-259 (1995).
82. Turturro A, Blank K, Murasko D, Hart R. Mechanisms of caloric restriction effecting aging and disease. Ann NY Acad Sci 719:159-170 (1994).