Mutational specificities of environmental carcinogens in the lacl Gene of Escherichia coli VII: The host‐mediated assay and its comparison with in vitro mutagenesis induced by 4‐(methylnitrosamino)‐1‐(3‐pyridyl)‐1‐butanone

Jianli Jiao, Barry W. Glickman, Maria Zielenska, Joseph B. Guttenplan, Liu‐Yu ‐Y Xin, Marshall W. Anderson

Research output: Contribution to journalArticle

Abstract

To investigate the influence of different types of metabolic activation (9,000 x g supernatant (S9) activation vs. a host‐mediated approach) on 4‐(methylnitrosamino)‐1‐(3‐pyridyl)‐1‐butanone (NNK)‐induced mutational specificity, we determined by DNA sequencing the distribution of forward mutations recovered in the N‐terminal region of the lacl gene of Escherichia coli. After activation with the S9 liver fraction from rats treated with Aroclor 1254, a diverse spectrum of mutations was recovered, with 55% of the events being G:C→A:T transitions. In contrast, after the host‐mediated assay in mice, G:C→A:T transitions accounted for over 94% of the mutations recovered. Generally, NNK metabolism can proceed through two distinct pathways, involving either α‐methyl or methylene hydroxylation. These two pathways produce different distributions of DNA damage. The difference in the mutational spectra we observed thus likely reflects the difference in the contributions of each pathway under the two different treatment conditions.

Original languageEnglish (US)
Pages (from-to)127-131
Number of pages5
JournalMolecular Carcinogenesis
Volume8
Issue number3
DOIs
StatePublished - 1993

Keywords

  • Mutational specificity
  • alkylating agents
  • host‐mediated assay

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research

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