Alternative mouse models for carcinogenicity assessment: Industry use and issues with pathology interpretation

Toxicologic Pathology

Volumn 38, Issue 1, 2010, Pages 43-50

  Long, Gerald G ^a   Morton, Daniel ^b   Peters, Terry ^c   Short, Brian ^d   Skydsgaard, Mikala ^e  

^a ELI LILLY AND COMPANY   (United States)

^b PFIZER INC   (United States)

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

^d ALLERGAN INC   (United States)

^e LAB Research Denmark   (Denmark)

Author keywords

Alternative models; Carcinogenesis; Mouse; Sarcoma

Indexed keywords

METHYLNITROSOUREA; PROTEIN P53;

CANCER MODEL; CARCINOGEN TESTING; CARCINOGENICITY; CHEMICAL CARCINOGENESIS; GENOTOXICITY; HISTOPATHOLOGY; NOMENCLATURE; NONHUMAN; PEER REVIEW; PRIORITY JOURNAL; REVIEW; SURVIVAL RATE; ANIMAL; DISEASE MODEL; EXPERIMENTAL NEOPLASM; METHODOLOGY; MOUSE; ONCOGENE RAS; PATHOLOGY; PHYSIOLOGY;

ANIMALIA; MUS;

ANIMALS; CARCINOGENICITY TESTS; DISEASE MODELS, ANIMAL; GENES, RAS; METHYLNITROSOUREA; MICE; NEOPLASMS, EXPERIMENTAL; TERMINOLOGY AS TOPIC; TUMOR SUPPRESSOR PROTEIN P53;

EID: 77952314409     PISSN: 01926233     EISSN: 15331601     Source Type: Journal    
DOI: 10.1177/0192623309354107     Document Type: Review

References (34)

1. Blanchard, K. T., Barthel, C., French, J. E., Holden, H. E., Mortez, R., Pack, F. D., Tennant, R. W., and Stoll, R.E. (1999). Transponderinduced sarcoma in the heterozygous p53+/- mouse. Toxicol Pathol 27, 519-527
2. Bolon, B., and Galbreath, E. (2002). Use of genetically engineered mice in exploratory toxicology. Int J Toxicol 21, 55-64.
3. Crissman, J. W., Goodaman, D. G., Hildebrandt, P. K., Maronpot, R. R., Prater, D. A., Riley, J. H., Seaman, W. J., and Thake, D. C. (2004). Best practices guideline: toxicologic pathology. Toxicol Pathol 32, 126-131
4. Deschl, U., Kittel, B., Rittinghausen, S., Morawietz, G., Kohler, M., Mohr, U., and Keenan C. (2002). The value of historical control data-scientific advantages for pathologists, industry and agencies. Toxicol Pathol 30, 80-87.
5. Doetschman, T. 1999. Interpretation of phenotype in genetically engineered mice. Lab Anim Sci 49, 137-143
6. EMEA. (2004). CHMP SWP conclusions and recommendations on the use of genetically modified animal models for carcinogenicity assessment. EMEA, CPMP/SWP/2592/02 Rev 1, London, June 23, 2004. Available at: http://www.emea.europa.eu/pdfs/human/swp/259202en.pdf, accessed April 12, 2009.
7. Floyd, E., Mann, P., Long, G., and Ochoa, R. (2002). The Trp53+/- hemizygous mouse in pharmaceutical development: Points to consider for pathologists. Toxicol Pathol 30, 147-156
8. Frith, C. H., Ward, J. M., Harleman, J. H., Stromberg, P. C., Halm, S., Inoue, T., and Wright, J. A. (2001). Hematopoietic systems. In International Classification of Rodent Tumors. The Mouse (U. Mohr, ed.), pp. 417-451, Springer, Berlin.
9. Gopinath, C. (1994). Spontaneous tumour rates: Their use to support rodent bioassays. Toxicol Pathol 22, 160-164
10. Hardisty, J. F. (1985). Factors influencing laboratory animal spontaneous tumor profiles. Toxicol Pathol 13, 95-104.
11. Haseman, J. K. (1992). Value of historical controls in the interpretation of rodent tumor data. Drug Inform J 26, 191-200.
12. Hoivik, D. J., Allen, J. S., Wall, H. G., Nold, J. B., Miller, R. T., and Santostefano, M. J. (2006). Studies evaluating the utility of N-methyl-Nnitrosourea as a positive control in carcinogenicity studies in the p53+/- mouse. Int J Toxicol 24, 349-356
13. Honchel, R., Rosenzweig, B. A., Thompson, K. L., Blanchard, K. T., Furst, S. M., Stoll, R. E., and Sistare, F. D. (2001). Loss of palindromic symmetry in Tg.AC mice with a nonresponder phenotype. Mol Carcinogen 30, 99-110.
14. ICH Guidance for Industry: S1B Testing for Carcinogenicity of Pharmaceuticals (1997). U.S. Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research (CDER).
15. Keenan, C., Elmore, S., Francke-Carroll, S., Kemp, R., Kerlin, R., Peddada, S., Pletcher, J., Rinke, M., Schmidt, S. P., Taylor, I., and Wolf, D. C. (2009). Best practices for use of historical control data of proliferative rodent lesions. Toxicol Pathol 37, 679-693
16. Korach, K. S. (1994). Insights from the study of animals lacking functional estrogen receptor. Science 266, 1524-1527
17. Le Calvez, S., Perron-Lepage, M.-F., and Burnett, R. (2005). Subcutaneous microchip-associated tumours in B6C3F1 mice: A retrospective study to attempt to determine their histogenesis. Exp Toxicol Pathol 57, 255-265
18. Lin, K., and Zhou, F. (2003). Statistical issues in review of carcinogenicity studies using transgenic mice. 2003 FDA/Industry Statistics Workshop, September 18-19, 2003, Bethesda, MD.
19. Long, G.G., Gries, C. L.,McGrath, J. P.,Young, J.K., andHoffman,W.P. (2001). Carcinogenic responses of heterozygous p53+/- knockout mice to orally administered cyclophosphamide. Toxicol Pathol 29 Suppl, 209-211
20. MacDonald, J., French, J. E., Gerson, R. J., Goodman, J., Inoue, T., Jacobs, A., Kasper, P., Keller, D., Lavin, A., Long, G., McCullough, B., Sistare, F. D., Storer, R., and van der Laan, J. W. (2004). The utility of genetically modified mouse assays for identifying human carcinogens: A basic understanding and path forward. Toxicol Sci 77, 188-194
21. Mahler, J. F., Flagler, N. D., Malarkey, D. E., Mann, P. C., Haseman, J. K., and Eastin, W. (1998). Spontaneous and chemically induced proliferative lesions in Tg.Ac transgenic and p53+/- heterozygous mice. Toxicol Pathol 26, 501-511
22. McConnell, E. E., Solleveld, H. A., Swenburg, J. A., and Boorman, G. A. (1986). Guidelines for combining neoplasms for evaluation of rodent carcinogenesis studies. J Natl Cancer Inst 76, 283-289
23. Mitsumori, K., Loizumi, H., Nomura, T., and Yamamoto, S. (1998). Pathological features of spontaneous and induced tumors in transgenic mice carrying a human prototype c-Ha-ras gene used for six-month carcinogenicity studies. Toxicol Pathol 26, 520-531
24. Mohr, U. (ed.). (2001). International Classification of Rodent Tumors. The Mouse. Springer, Berlin.
25. Morton, D., Bailey, K. L., Stout, C. L., Weaver, R. J., White, K. A., Lorenzen, M. K., and Ball, D. J. (2008). N-methyl-N-nitorsuriea (MNU): A positive control chemical for p53+/- mouse carcinogenicity studies. Toxicol Pathol 36, 926-931
26. Risma, K. A., Clay, C. M., Nett, T. M., Wagner, T., Yun, J., and Nilson, J. H. (1995). Targeted overexpression of luteinizing hormone in transgenic mice leads to infertility, polycystic ovaries, and ovarian tumors. Proc Natl Acad Sci USA 92, 1322-1326
27. Robinson, D. E., and MacDonald, J. S. (2001). Background and framework for ILSI's collaborative evaluation program on alternative models for carcinogenicity assessement. Toxicol Pathol 29(Suppl), 13-19.
28. Storer, R. D., French, J. E., Haseman, J., Hajian, G., LeGrand, E.K., Long, G.G., Mixson, L. A., Ochoa, R., Sagartz, J. E., and Soper, K. A. (2001). P53+/- hemizygous knockout mouse: overview of available data. Toxicol Pathol 29(Suppl), 30-50.
29. STP (2009). INHAND Documents. Available at: http://www.toxpath.org/ inhand.asp. Accessed April 15, 2009.
30. Takaoka, M., Sehata, S., Maejima, T., Imai, T., Torii, M., Satoh, H., Toyosawa, K., Tanakamaru, Z.-Y., Adachi, T., Hisada, S., Ueda, M., Ogasawara, H., Matsumoto, M., Kobayashi, K., Mutai, M., and Usui, T. (2003). Interlaboratory comparison of short-term carcinogenicity studies using CB6F1-rasH2 transgenic mice. Toxicol Pathol 31, 191-199
31. Tennet, B. J., and Beamer, W. G. (1986). Ovarian tumors not induced by irradiation and gonadotropins in hypogonadal mice. Biol Reprod 34, 751-760
32. Usui, T., Mutai, M., Hisada, S., Takoaka, M., Soper, K., McCullough, B., and Alden, C. (2001). CB6F1-rasH2 mouse: Overview of available data. Toxicol Pathol 29(Suppl), 90-108.
33. van Zwieten, M. J., Majka, J. A., Peter, C. P., and Burek, J. D. (1988). The value of historical control data. In ILSI Monographs: Carcinogenicity-The Design, Analysis and Interpretation of Long-Term Animal Studies (H. C. Gries and J. L. Ciminera, eds.), pp. 39-51, Springer-Verlag, New York.
34. Weaver, J. L., Contrera, J. F., Rosenzweig, B. A., Thompson, K. L., Faustino, P. J., Strong, J. M., Ellison, C. D., Anderson, L. W., Prasanna, H. R., Long-Bradley, P. E., Lin, K. K., Zhang, J., and Sistare, F. D. (1998). An evaluation of the hemizygous transgenic Tg.AC mouse for carcinogenicity testing of pharmaceuticals. I. Evidence for a confounding nonresponder phenotype. Toxicol Pathol 26, 532-540