Mutagenicity of isomeric alkanediazotates, precursors for ultimate alkylating species of carcinogenic N-nitroso compounds

Satoko Ukawa-Ishikawa, Atsuko Sawada, Keiko Kasuya, Masataka Mochizuki

Research output: Contribution to journalArticlepeer-review

9 Citations (Scopus)

Abstract

Alkanediazohydroxides are common key intermediates in carcinogenesis and mutagenesis of N-nitroso compounds, which are widely found in human environment. Mutagenicity of (E)- and (Z)-potassium alkanediazotates, as precursors of corresponding alkanediazohydroxides were evaluated to investigate the effect of geometric isomerism and also the effect of alkyl groups on their biological activity. Mutagenicity of N-nitroso-N-alkylureas which spontaneously produce alkanediazohydroxides after non-enzymatic hydrolysis were also tested in comparison to that of the corresponding diazotates and other activated chemical species of N-nitrosamines. When the mutagenicity was assayed in three microbial strains, Salmonella typhimurium TA1535, and Escherichia coli WP2 and WP2 uvrA, the order of mutagenic potency of the compounds with the same alkyl group was as follows, (E)-diazotates > (Z)-diazotates > nitrosoureas. The effect of alkyl groups on the mutagenic potency was different in Salmonella strain and in E. coli strains, and this result could be explained by the efficiency of O6-alkylguanine-DNA alkyltransferase. In each bacterial strain, this effect of alkyl groups was similar in mutagenicity induced by (E)- and (Z)-diazotates, N-nitroso-N-alkylureas and other activated N-nitrosodialkylamines such as α-hydroxy nitrosamines. The geometrical isomerism affected the mutagenicity of (E)- and (Z)-potassium alkanediazotates, and the result suggested that alkanediazohydroxides react through diazonium ions in a cage rather than through free alkyldiazonium ions which have no geometrical isomerism. Our results confirmed that (E)-potassium alkanediazotates, (Z)-potassium alkanediazotates and N-nitroso-N-alkylureas all decomposed through diazohydroxides, and that alkanediazohydroxides are the active alkylating species of N-nitroso compounds, and also that the geometrical isomerism is important for carcinogenic N-nitroso compounds to show their biological activity.

Original languageEnglish
Pages (from-to)99-107
Number of pages9
JournalMutation Research - Genetic Toxicology and Environmental Mutagenesis
Volume412
Issue number1
DOIs
Publication statusPublished - 1998 Jan 13

Keywords

  • Alkanediazotate
  • Geometrical isomerism
  • Mutagenicity
  • N-nitroso compound
  • Ultimate alkylating species

ASJC Scopus subject areas

  • Genetics
  • Health, Toxicology and Mutagenesis

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