Involvement of the drug efflux protein TolC in mutagenicity induced by MNNG or Trp-P-2

Eizo Takahashi, Keinosuke Okamoto, Sakae Arimoto, Hiroyasu Yamanaka, Tomoe Negishi

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

In the development of mutation assay systems, a number of approaches have been performed with a particular view to improve sensitivity. The inhibition of mutagen-efflux from tester bacteria might lead to increased mutagenic activity as the concentration of mutagen increases inside the cell. In this study, we constructed a series of Escherichia coli CC strains lacking the TolC protein to determine if mutation is actually enhanced by the inhibition of mutagen reflux. TolC is an outer-membrane protein that forms part of an excretion system in E. coli. The frequency of induction of mutations by N-methyl-N′-nitro-N-nitrosoguanidine (MNNG), N-ethyl-N′-nitro-N-nitrosoguanidine (ENNG) and ethyl methanesulfonate (EMS) were significantly higher in TolC-deficient strain KA796-1/CC102 than in TolC-proficient strains, especially that of MNNG was seven times higher and detected at lower doses than in the parent strain. In a KA796-1/CC108 TolC-deficient strain, mutation induced by Trp-P-2 was detected at significant levels, even at low doses that did not induce detectable levels of mutation in the parent strain KA796/CC108. When the wild-type E. coli tolC gene was introduced into a strain lacking the gene, TolC function was restored and the frequency of induction by MNNG became similar to that of the wild-type. In contrast, introduction of a mutant tolC gene did not complement the TolC deficiency and the frequency of MNNG-induced mutations remained high. These results suggest that some mutagens are excreted at least in part via the TolC system, and that the lack of functional TolC increases the susceptibility of bacteria to many mutagens.

Original languageEnglish
Pages (from-to)42-50
Number of pages9
JournalMutation Research - Genetic Toxicology and Environmental Mutagenesis
Volume605
Issue number1-2
DOIs
Publication statusPublished - Jun 16 2006

Fingerprint

Methylnitronitrosoguanidine
Mutagens
Mutation
Pharmaceutical Preparations
Escherichia coli
Proteins
Ethyl Methanesulfonate
Genes
Bacteria
Mutation Rate
Membrane Proteins
3-amino-1-methyl-5H-pyrido(4,3-b)indole

Keywords

  • Drug efflux
  • E. coli
  • MNNG
  • Mutation
  • TolC
  • Trp-P-2

ASJC Scopus subject areas

  • Health, Toxicology and Mutagenesis
  • Genetics
  • Medicine(all)

Cite this

Involvement of the drug efflux protein TolC in mutagenicity induced by MNNG or Trp-P-2. / Takahashi, Eizo; Okamoto, Keinosuke; Arimoto, Sakae; Yamanaka, Hiroyasu; Negishi, Tomoe.

In: Mutation Research - Genetic Toxicology and Environmental Mutagenesis, Vol. 605, No. 1-2, 16.06.2006, p. 42-50.

Research output: Contribution to journalArticle

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