Recently, the use of selected genetically altered mouse models in the detection of carcinogens after short-term chemical exposures has been evaluated. Studies of several chemicals conducted by the National Toxicology Program in Tg.AC transgenic and heterozygous p53-deficient mice have been completed recently and represent a major contribution to this effort, as well as the largest accumulation to date of toxicologic pathology data in these 2 lines of mice. The purpose of this report is to describe the proliferative target organ effects observed in this set of studies, as well as to present the tumor profile in the control groups of this data set. These findings provide a comprehensive toxicologic assessment of these 2 genetically altered mouse strains, which are of emerging importance in toxicologic pathology.
1. Asano S, Trempus CS, Spalding JW, Tennant RW, and Battalora MS (1998). Morphological characterization of spindle cell tumors induced in transgenic Tg.AC mouse skin. Toxicol. Pathol.26: 512–519 (this issue).
2.
2. Bauluz C, Larcher F, Ballestin C, Grande T, and Jorcano J (1994). Augmented expression of cytokines in mouse epidermal tumor cells and its possible involvement in the induction of hematopoietic alterations. Mol. Carcinog.. 11: 155–163.
3.
3. Cardiff RD, Leder A, Kuo A, Pattengale PK, and Leder P (1993). Multiple tumor types appear in a transgenic mouse with the ras oncogene. Am. J. Pathol.. 142: 1199–1207.
4.
4. Chhabra RS, Huff JE, Schwetz BS, and Selkirk J (1990). An overview of prechronic and chronic toxicity/carcinogenicity experimental study designs and criteria used by the National Toxicology Program. Environ. Health Perspect.. 86: 313–321.
5.
5. Cline MJ (1994). The molecular basis of leukemia. N. Engl. J. Med.. 330: 328–336.
6.
6. Donehower LA, Harvey M, Vogel H, McArthur MJ, Montgomery CA, Park SH, Thompson T, Ford RJ, and Bradley A (1995). Effects of genetic background on tumorigenesis in p53-deficient mice. Mol. Carcinog.. 14: 16–22.
7.
7. Dunnick JK, Hardisty JF, Herbert RA, Seely JC, Furedi-Machacek EM, Foley JF, Lacks GD, Stasiewicz S, and French JE (1997). Phenolphthalein induces thymic lymphomas accompanied by loss of the p53 wild type allele in heterozygous p53-deficient mice. Toxicol. Pathol.. 25: 533–540.
8.
8. Eastin WC, Haseman JK, Mahler JF, and Bucher JR (1998). The National Toxicology Program evaluation of genetically altered mice as predictive models for identifying carcinogens. Toxicol. Pathol.26: 461–473 (this issue).
9.
9. Frith CH, Ward JM, and Chandra M (1993). The morphology, im-munohistochemistry, and incidence of hematopoietic neoplasms in mice and rats. Toxicol. Pathol.. 21: 206–218.
10.
10. Hansen LA, Trempus CS, Mahler JF, and Tennant RW (1996). Association of tumor development with increased cellular proliferation and transgene overexpression, but not c-Ha-ras mutations, in v-Ha-ras transgenic Tg.AC mice. Carcinogenesis. 17: 1825–1833.
11.
11. Hennings H, Glick AB, Lowry DT, Krsmanovic LS, Sly LM, and Yuspa SH (1993). FVB/N mice: An inbred strain sensitive to the chemical induction of squamous cell carcinomas in the skin. Carcinogenesis. 14: 2353–2358.
12.
12. Huff J, Cirvello J, Haseman J, and Bucher J (1991). Chemicals asociated with site-specific neoplasia in 1394 long-term carcinogenesis experiments in laboratory rodents. Environ. Health Perspect.. 93: 247–270.
13.
13. Jain NC (1993). The leukemias: General aspects. In: Essentials of Veterinary Hematology, NC Jain (ed). Lea and Febiger, Philadelphia, pp. 326–333.
14.
14. Kadin M, Butmarc J, Elovic A, and Wong D (1993). Eosinophils are the major source of transforming growth factor beta 1 in nodular sclerosing Hodgkin's disease. Am. J. Pathol.. 142: 11–16.
15.
15. Kemp CJ, Wheldon T, and Balmain A (1994). p53-Deficient mice are extremely susceptible to radiation-induced tumorigenesis. Nat. Genet.. 8: 66–68.
16.
16. Liu ET (1990). The role of ras gene mutations in myeloproliferative disorders. Clin. Lab. Med.. 10: 797–807.
17.
17. Long RE, Knutsen G, and Robinson M (1986). Myeloid hyperplasia in the SENCAR mouse: Differentiation from granulocytic leukemia. Environ. Health Perspect.. 68: 117–123.
18.
18. Mahler JF, Stokes W, Mann PC, Takaoka M, and Maronpot RR (1996). Spontaneous lesions in aging FVB/N mice. Toxicol. Pathol.. 24: 710–716.
19.
19. Marsella JM, Liu BL, Vaslet CA, and Kane AB (1997). Susceptibility of p53-deficient mice to induction of mesothelioma by cro-cidolite asbestos fibers. Environ. Health Perspect.105(suppl. 5): 1069–1072.
20.
20. Spalding JW, Momma J, Elwell MR, and Tennant RW (1993). Chemically induced skin carcinogenesis in a transgenic mouse line (TG.AC) carrying a v-Ha-ras gene. Carcinogenesis. 14: 1335–1341.
21.
21. Tennant RW, French JE, and Spalding JW (1995). Identifying chemical carcinogens and assessing potential risk in short-term bio-assays using transgenic mouse models. Environ. Health Perspect.. 103: 942–950.
22.
22. Wright JT, Hansen L, Mahler J, Szczesniak C, and Spalding JW (1995). Odontogenic tumours in the v-Ha-ras (TG.AC) transgenic mouse. Arch. Oral Biol.. 40: 631–638.
