Nitrous acid mutagenesis of duplex DNA as a three-component system

Harvey F. Thomas, Philip E. Hartman, Maria Mudryj, Diane L. Brown

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

Purified native Hemophilus influenzae DNA is relatively insusceptible to nitrous acid (NA) mutagenesis in vitro, but is readily mutated following denaturation. NA mutagenicity for duplex DNA is significantly increased in the presence of various alcohols, glycols, phenols or primary amines. Phenolextracted DNA contains dissociable contaminants of low molecular weight that enhance NA mutagenesis. Enhancement of NA mutagenesis by phenol and by spermine is due to the formation of unstable molecular species. We propose that reactive organic nitroso compounds are formed which then serve as delivery vehicles to promote mutagenicity of native DNA, perhaps via transnitrosation reactions. Similar reactions probably occur in vivo to promote NA-induced base substitution (but not frameshift) mutations in Salmonella typhimurium and in Escherichia coli. The possible significance of these observations to carcinogenesis is discussed.

Original languageEnglish (US)
Pages (from-to)129-151
Number of pages23
JournalMutation Research - Fundamental and Molecular Mechanisms of Mutagenesis
Volume61
Issue number2
DOIs
StatePublished - 1979
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Biology
  • Health, Toxicology and Mutagenesis
  • Medicine(all)

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