Additive Mutagenic Effects of DNA Damages Induced by Multiple Mutagens at Virtually Non-mutagenic Dose Level of Each

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DNA damages provoked by the six mutagens (furyl-framide, MX, 4-nitroquinoline N-oxide, sodium azide, 1-nitropyrene, and captan) used in the present study have been known to subject to the nucleotide excision repair system. Therefore, they induced base-substitution mutations much more efficiently in Salmonella typhimurium TA100 (hisG46, rfa, uvrB/pKM101), a strain deficient in nucleotide excision repair, than in TA1975P (hisG46, rfa/pKM101). Doses below undetectable level in the reverse mutation assay were selected as those that were apparently mutagenic to the repair-deficient strain TA100 but not to the repair-proficient strain TA1975P in this study. Then, the six mutagens were mixed at virtually non-mutagenic dose level of each and a possible combined mutagenic effect was investigated. A significant and reproducible increase in the number of revertants in TA1975P was observed with combined mutagens. The results suggest that DNA adduct formation at virtually non-mutagenic dose level was additive, with the total amount reflecting the mutagenicity.
2007-11-30