Difference in sensitivity of Salmonella typhimurium strains to alkylating agents

243 There is still suspicion whether carcinogenic or mutagenic effects of saccharin are due to its impurities. Thus, chromosome damaging effects of o- or p-toluenesulfonamide and o-sulfobenzoic acid on CHO-K1 cells in vitro were studied. The cells were treated with DMSO (50 pl/ml), o-toluenesulfonamide (0.9, 14, 200, 400 vg/ml), p-toluenesulfonamide (14, 200,400 vg/ml), o-sulfobenzoic acid (14, 200, 400 pg/ml) and a mixture of these three impurities (14 pg/ml each). Furthermore, untreated and saccharin-Na treated (20 mg/ml) groups were settled for negative and positive controls. Saccharin-Na used in these studies was of high purity (99.93%) and contained 45 ppm of o-toluenesulfonamide. After 24-h treatment, induced chromosome aberrations were observed only in the saccharin-Na group (breaks, 38 per 200 cells; gaps, 38 per 200 cells; P < 0.001 each). There is no significant difference in frequency of aberrant cells between other treated groups and the negative control group.

14 Matsushima, T., A. Shirai, M. Sawamura, K. Umezawa and T. Sugimura, Department of Molecular Oncology, Institute of Medical Science, University of Tokyo, Tokyo (Japan) Difference in sensitivity of Salmonella typbimurium strains to alkylating agents

Salmonella typhimurium TA1535, TA1537, TA1538, TA100 and TA98 are widely used in screening of environmental muta-carcinogens. These tester strains all lack the capacity for excision repair of DNA-damage and are generally more sensitive to muta-carcinogens than strains with the repair capacity. However, it was shown that S. typhimurium hisG46, which is a repair-positive strain, showed a higher sensitivity to cycasin than TA1535 or TA100, after activation of the drug to methylazoxymethanol by ~-glucosidase. We studied the sensitivities of various Salmonella tester s t r a i n s - repair-positive strains such as hisG46, TA1975 and TA92, and repair-deficient strains such as TA1950, TA1535 and TA100 -- to several methylating and ethylating agents. Repair-positive strains showed higher sensitivity than repair-deficient strains to the methylating agents, N-methyl-N'-nitro-N-nitrosoguanidine, N-methyl-Nnitrosourea, dimethylsulfate, cycasin (methylazoxymethanol) and dimethylnitrosamine. Conversely repair-deficient strains: showed higher sensitivity to the ethylating agents, N-ethyl-N'-nitro-N-nitrosoguanidine, N-ethyl-N-nitrosourea and diethylsulfate. Repair-deficient and repair-positive strains showed similar sensitivities to methyl methanesulfonate, ethyl methanesulfonate and diethylnitrosamine.

15 Morita, K., T. Inoue and T. Kada, Department of Induced Mutation, National Institute of Genetics, Mishima, Shizuoka-ken 411 {Japan)