Mutagenicity of potassium alkanediazotates in Chinese hamster V79 cells and their alkylating activity

Satoko Ishikawa, Masako Seki, Masataka Mochizuki

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

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 activin, alkylating activity towards nicotinamide in an aqueous phosphate buffer system was evaluated as an index of the chemical reactivity of diazorates. Using a fluorometric HPLC method, alkylated nicotinamides were detected with high sensitivity in the reaction with all diazorates tested. The alkylating 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 V79 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.

Original languageEnglish
Pages (from-to)577-581
Number of pages5
JournalBiological and Pharmaceutical Bulletin
Volume22
Issue number6
Publication statusPublished - 1999

Fingerprint

Nitroso Compounds
Niacinamide
Cricetulus
Potassium
Isomerism
Activins
Nitrosamines
Salmonella typhimurium
Mammals
Buffers
Phosphates
High Pressure Liquid Chromatography
DNA

Keywords

  • Alkanediazotate
  • Alkylating activity
  • Chinese hamster cells
  • Geometrical isomerism
  • Mutagenicity
  • N-nitroso compound

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology, Toxicology and Pharmaceutics(all)

Cite this

Mutagenicity of potassium alkanediazotates in Chinese hamster V79 cells and their alkylating activity. / Ishikawa, Satoko; Seki, Masako; Mochizuki, Masataka.

In: Biological and Pharmaceutical Bulletin, Vol. 22, No. 6, 1999, p. 577-581.

Research output: Contribution to journalArticle

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AB - 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 activin, alkylating activity towards nicotinamide in an aqueous phosphate buffer system was evaluated as an index of the chemical reactivity of diazorates. Using a fluorometric HPLC method, alkylated nicotinamides were detected with high sensitivity in the reaction with all diazorates tested. The alkylating 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 V79 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.

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