Combined effects of chemicals on mammalian cells in culture, II. Effects of ethyl methanesulfonate (EMS) and arabinosyl cytosine (Ara-C) on mutation induction

281 MNU: 20-40 times more sensitive than the parent strain. On the other hand, it showed no enhanced mutagenesis to the action of other alkylating agents, UV irradiation, 4NQO or AF2. Microscopically the cells appear spherical. T h e strain grows at temperatures lower than that at which the parent strain grows; i.e., at 30°C where the parent strain cannot grow. Results of these tests show a similarity of Sd-4c(TC) to Sd-B(TC). According to recent reports, insertion of T n l 0 transposon encoding TC resistance into host chromosomes can induce mutations, some of which produce mutants having high mutabilities to alkylating agents. We assume that Sd-4c(TC) and Sd-B(TC) resemble these mutant strains reported.

50 Shinkawa-Tachi, K., K. Morimoto, A. Koizumi and Y. Kurodal, Department of Public Health, Faculty of Medicine, University of Tokyo, Tokyo 113 and 1 National Institute of Genetics, Mishima, Shizuoka 411 (Japan) Combined effects of chemicals on mammalian cells in culture, II. Effects of ethyl methanesulfonate (EMS) and arabinosyl cytosine (Ara-C) on mutation induction EMS has a strong mutagenic effect on Chinese hamster V79 cells (induction of 6-thioguanine resistance), but for Ara-C there has been a controversy as to whether it is mutagenic or not. In this study, Ara-C had no detectable effect in inducing mutations up to a concentration of 5 x 10 - 4 M. The mutation frequencies found in the combined action of EMS and Ara-C on V79 cells, both in the simultaneous and the sequential treatments, were significantly higher than that obtained with EMS alone. These results indicate that Ara-C has an enhancing effect on mutations induced by EMS.

51 Sofuni, T., M. Hayashi, H. Shimada 1, y . Ebine 1, A. Matsuoka, S. Sawada and M. Ishidate Jr., Division of Mutagenesis, National Institute of Hy-

gienic Sciences, Tokyo 158 and 1 Daiichi Seiyaku Co., Ltd., Tokyo 132 (Japan) Sex difference in the micronucleus induction by benzene in mice Benzene is known to show a sex-dependent difference in the micronucleus induction in mice. One of the factors causing the sex difference seems to be different metabolic activity between males and females. In the present study, metabolites of benzene, such as phenol, catechol and hydroquinone were examined to see whether these chemicals show a sex difference in the induction of micronuclei. Phenol induced micronuclei at doses of 150 and 200 mg/kg, but there was no statistically significant difference between males and females. Hydroquinone also induced micronuclei at 70 and 100 mg/kg, but at 70 m g / k g female mice showed a remarkably higher frequency of micronuclei than did male mice. On the other hand, catechol did not show any significant increase in the frequency of micronuclei The induction of micronuclei by benzene was significantly inhibited by 7,8-benzoflavone, an inhibitor of cytochrome P-450 activity, in male but not in female mice. Another inhibitor, metyrapone did not show any apparent influence on the micronucleus induction by benzene. The above findings suggest that metabolic activities in the pathway from benzene to phenol through benzene epoxide may be different in males and in females, and that this difference may be related to the cytochrome P450 monooxygenase which is induced by 3-methylcholanthrene and inhibited by 7,8-benzoflavone.

52 Takahashi, M., N. Kinae, I. Tomita, K. Wakabayashi 1, M. Nagao 1, S. Sato I and T. Sugimura l, Shizuoka College of Pharmacy, Oshika, Shizuoka 422 and 1 National Cancer Center Research Institute, Chuo-ku, Tokyo 104 (Japan) Quantification of heterocyclic amines in cooked foods