Investigation of the dominant-lethal assay. I. Dominant-lethal effects of chemical compounds after long-term administration into male mice

242 cells were most suitable for giving the highest colony-forming activity in primary culture. Among lung cells from embryos at various gestation stages examined, cells from 13-week-old embryos gave the highest colony-forming activity. Lung cells from embryos at various ages were cultured in medium containing 30 pg/ml 8-azaguanine (8AG). The number of 8AG-resistant colonies formed was scored and the frequency of 8AG-resistant cells in embryonic lung tissue was estimated. The frequency of m u t a n t cells in an 8-week-old embryo was 1.6 X 10 -3. The frequency increased gradually in embryos at more advanced stages. In lung cells from a 10-week-old embryo the frequency was 1.8 X 10 -3, in a 13-week-old embryo it was 2.0 X 10 -3, in an 18-week-old embryo it was 7.9 X 10 -3 and in a 24-week-old embryo it was 15.0 X 10 -3. The m u t a t i o n frequency (Yi) was found to be correlated theoretically to the gestation stages in week (ti) of embryos in the formula, Yi = 0.14 X 10 -3 ti. These results indicate that this procedure may be useful for practical monitoring of the human environmental mtttagens.

12 Masubuchi, M., A. Takahashi, S. Yoshida, H. Ando, Y. Kubo and K. Hiraga, T o k y o Metropolitan Research Laboratory of Public H e a l t h , T o k y o (Japan)

Investigation of the dominant-lethal assay. I. Dominant-lethal effects of chemical compounds after long-term administration into male mice The relationship between acute and long-term administration in the dominant-lethal assay on JCL-ICR mice were studied. In these studies, ethyl methanesulfonate (EMS; 42 ~ 200 mg/kg, 7 groups) or mitomycin C (MMC; 0.37 ~ 1.75 mg/kg, 7 groups) were administered i.p. every 4 days, for 4, 6 and 8 weeks (throughout the entire cycle of spermatogenesis). At the end of the treatment period, a male mouse was mated with 2 untreated virgin females. Total number of animals used in this study was 1200. The dominant-lethal effects were observed at lower dose of the long-term administration than that of the single injection and with clear dose relationships. In EMS groups, no changes of frequency of the d o m i n a n t lethality was found among each mating time. While in MMC groups the treatment times become longer, the frequency of the induced dominant lethals becomes lower. The results presented here indicate that the long-term administration of chemical compounds was a useful m e t h o d in th~ dominant-lethal assay.

13 Masubuchi, M., S. Nawai,. M. Hirokado and K. Hiraga, T o k y o Metropolitan Research Laboratory of Public Health, T o k y o (Japan)

Lack o f the cytogenetic effects of saccharin impurities on CHO-K1 cells