Inhibition of N-nitrosodimethylamine metabolic activation by dimethyl sulfoxide or 5,5-dimethyl-1-pyrroline-N-oxide

264

was approximately 1.63 times more than control (3593 cpm/100 flies). This result showed the oxidative damage in living Drosophila melanogaster by feeding of hydrogen peroxide. Mutagenic activity and DNA damaging activity of hydrogen peroxide were negative at the above concentration to Drosophila melanogaster. Catalase activity of pupae was increased to 1.58 times by feeding the medium containing 0.08% of hydrogen peroxide. It was considered that antioxidant function such as catalase appears to protect against oxidative damage to DNA in Drosophila melanogaster.

vating mixture. Simultaneously hydroxyl radical formation was observed as DMPO-OH spin adduct. The relative peak height of hydroxyl radical to manganase standard decreased linearly with addition of DMPO. The role of hydroxyl radical formed in preincubation of $9 mix and NDMA was hydrogen abstraction to give a carbon radical intermediate, and to hydroxylate the carbon radical to give the hydroxymethyl group. It is just the monooxygenation of NDMA. Successive hydrogen abstraction was repeated to give a methylenoxyl radical. The resulting N-nitroso-N'methyl-N-methylenoxyl radical is very unstable for its dinitrogen releasing and formaldehyde releasing. The proposed scheme is as given underneath. The metabolic activation of NDMA was inhibited with hydroxyl radical scavenging.

12 Furukawa, H., K. Kawai, M. Toyohara ~ and J. Ebata a, Faculty of Pharmaceutical Sciences, Meijo University, 150 Yagotoyama, Tempaku-ku, Nagoya 468 and a Faculty of Science of Living, Osaka City University, 3-3-138 Sugimoto, Sumiyoshi-ku, Osaka 558, Japan

13 Hakura, A., H. Mochida, Y. Tsutsui, Y. Sugihara, S. Kondoh and K. Yamatsu, Department of Drug Safety Research, Eisai Co., Ltd., 1-3 Tokodai, 5-chome, Tsukuba-shi, Ibaraki 300-26, Japan

Inhibition of N-nitrosodimethylamine metabolic activation by dimethyl sulfoxide or 5,5-dimethyl1-pyrroline-N-oxide

Mutagenicity of naphthoquinones Salmonella tester strains

The mutagenic activity of N-nitrosodimethylamine (NDMA) was suppressed by addition of dimethyl sulfoxide (DMSO) or 5,5-dimethyl-1pyrroline-N-oxide (DMPO) in the metabolic acti-

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