Mutagenicity of Potassium Alkanediazotates in Chinese Hamster V79 Cells and Their Alkylating Activity
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概要
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Alkanediazohydroxides are the key intermediates of carcinogenic N-nitroso compounds, and exist as geometrical isomers. In this paper, the mutagenicity and cytotoxicity of (E)- and (Z)-potassium alkanediazotates, precursors of alkanediazohydroxides, in Chinese hamster V79 cells were investigated. Mutagenic and cytotoxic activities of (E)-diazotates were dose-dependent, and activity decreased with an increase in the alkyl chain length; methyl>ethyl>propyl, butyl. On the other hand, (Z)-diazotates were less mutagenic and cytotoxic than(E)-diazotates, however (Z)-potassium methanediazotate did show weak mutagenicity. To compare chemical reactivity with biological activity, alkylating activity towards incotinamide in an aqueous phosphate buffer system was evaluated as an index of the chemical reactivity of diazotates. Using a fluorometric HPLC method, alkylated nicotinamides were detected with high sensitivity in the reaction with all diazotates tested. The alkylting activity of (Z)-methanediazotate was higher than that of the corresponding (E)-diazotate, but the other isomers with ethyl, propyl and butyl groups had similar reactivity under the conditions used. The activity decreased by increasing the alkyl chain-length, which correlated well with the mutagenicity in V97 cells and also with that in Salmonella typhimurium, which we reported earlier. The results for (E)-diazotates were similar to the corresponding N-nitroso-N-(hydroxymethyl)alkylamines, further supporting the notion that α-hydroxy nitrosamines decompose through alkanediazohydroxide and alkylate DNA, and suggests that geometrical isomerism influences the carcinogenicity of N-nitroso compounds in mammals.
- 公益社団法人日本薬学会の論文
- 1999-06-15
著者
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MOCHIZUKI Masataka
Kyoritsu University of Pharmacy
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Ukawa-ishikawa Satoko
Kyoritsu College Of Pharmacy
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SEKI Masako
Kyoritsu University of Pharmacy
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Seki Masako
Kyoritsu College Of Pharmacy
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Mochizuki M
Daiichi Pharmaceutical Co. Ltd. Tokyo Jpn
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Mochizuki Masataka
Kyoritsu College Of Pharmacy
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Ukawa Ishikawa
Kyoritsu College of Pharmacy
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