Mutational response at the splenic T-Lymphocyte hprt locus in mice treated as neonates: Contrasting effects of the carcinogens N-ethyl-N-nitrosourea, dimethylnitrosamine, and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine
✍ Scribed by S. Balachandra Dass; Robert H. Heflich; Daniel A. Casciano
- Publisher
- John Wiley and Sons
- Year
- 1998
- Tongue
- English
- Weight
- 138 KB
- Volume
- 31
- Category
- Article
- ISSN
- 0893-6692
No coin nor oath required. For personal study only.
✦ Synopsis
The newborn mouse tumorigenicity assay, which reached 155.1 1 10 06 following a cumulative dose involves the treatment of animals during the first two of 49 mg ENU/kg body weight and 172.3 1 10 06 weeks after birth and monitoring tumor induction following a cumulative dose of 142 mg ENU/kg. after a year, has been suggested as a cost-and These results show that TG r lymphocyte mutations can time-effective alternative to the conventional two-be induced and measured in mice treated as neoyear rodent bioassay. In order to evaluate whether nates and that the induced MFs found for mice treated or not lymphocyte hprt mutant induction is an accu-neonatally with ENU are comparable with frequenrate predictor of carcinogenicity in the assay, we cies reported for the treatment of adult animals determined the frequencies of 6-thioguanine-resis-with the same chemical. In contrast, treatment with tant (TG r ) lymphocytes in the spleens of mice neona-the promutagenic and procarcinogenic compounds tally treated with the carcinogenic mutagens N-ethyl-DMN (at a maximum concentration of 10.5 mg/kg) N-nitrosourea (ENU), dimethylnitrosamine (DMN), and PhIP (26.2 mg/kg) did not result in an increase and 2-amino-1-methyl-6-phenylimidazo [4,5-b]pyridine in lymphocyte MF, suggesting that reactive metabo-(PhIP). Male C57BL/6 pups were injected on post-lites of these compounds may not be reaching cells natal days 8 and 15, and the frequency of TG r that are sensitive for mutation fixation. The results T-lymphocytes was measured in groups of three ani-indicate that the lymphocyte hprt assay may fail to mals, sacrificed periodically up to 31 weeks post-predict the carcinogenicity of some test chemicals in treatment. Compared to background frequencies the neonatal mouse bioassay.