The Effect of Nicotinamide on the Mutagenicity of Various Alkylating Agents

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概要

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• The effect of nicotinamide on 7 kinds of mutagenic alkylating agents was investigated in Salmonella typhimurium TA100 without S9 mix, and its mechanism was studied. The mutagenic potency of alkylating agents other than N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) was reduced to less than 50% by the addition of about 50-fold molar ratio of nicotinamide to alkylating agent. The mutagenic potency of MNNG was only reduced to 60-70% by the addition of more than 200-fold molar ratio of nicotinamide. To investigate the mechanism of the suppressive effect of nicotinamide, alkylating agents (1.0 μmol) (methyl methanesulfonate and dimethyl sulfate) were reacted with nicotinamide (1.0 μmol) alone or together with DNA or 5 kinds of nucleotides in phosphate buffer (pH 7.4) at 30℃ for 24 h, and the resulting N^1-methylnicotinamide (NMN) was analyzed by HPLC with fluorometric detection after derivatization. With the addition of DNA (0.2 molar ratio or more), the amount of NMN by methyl methane-sulfonate was reduced to 80% compared with nicotinamide alone, whereas that by dimethyl sulfate was unchanged. With the addition of nucleotides like guanosine-5'-phosphate, the amount of NMN by methyl methanesulfonate was reduced to 75%, whereas no reducing effect was seen by the other 4 nucleotides. The present results strongly suggest that nicotinamide is more easily alkylated than nucleic bases in DNA or nucleotides by methyl methanesulfonate and dimethyl sulfate, and that nicotinamide scavenged alkyl species derived from them, thereby showing a suppressive effect on the mutagenicity of alkylating agents. In MNNG, nicotinamide did not act as des-mutagen in Salmonella assay.

• 公益社団法人日本薬学会の論文
• 1992-10-31

著者

• 渡辺 徹志

  Kyoto Pharmaceutical University

• 平山 晃久

  Kyoto Pharmaceutical University

• 中田 晴美

  Kyoto Pharmaceutical University

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