Induction of SOS-independent mutations by benzo[a]pyrene treatment in Escherichia coli cells deficient in MutY or MutM DNA glycosylases: possible role of oxidative lesions.
The induction of SOS-independent mutations by exposure to benzo[a]pyrene (BaP) was screened in Escherichia coli strains lacking SOS mutagenesis proteins and deficient in MutY or MutM glycosylases, which prevent mutations by 8-hydroxyguanine (GO lesion). Mutagenicity assays, performed in the presence of S9 mix, indicated a great increase in the reversion of the trpE65 ochre mutation in both mutY and mutY mutM strains, whereas a lower increase was observed in a mutM strain. This mutability by BaP was observed in either uvr- or uvr+ strains. Moreover, it was increased when strains carried a deletion of the oxyR gene that abolished the OxyR response to oxidative stress, and reduced in the presence of the oxyR2 allele that rendered constitutive such response. It is suggested that SOS-independent mutations in cells treated with BaP arise from adenine/GO mispairs. The interaction of radical scavengers with BaP ultimate metabolites could cause oxidative stress capable of producing GO lesions. Strains lacking mutagenesis proteins and deficient in base excision repair systems, such as those dependent on MutY and MutM glycosylases, could be useful for screening the induction of SOS-independent mutations.
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Instituto de Investigaciones Citológicas, Fundación Valenciana de Investigaciones Biomédicas, Spain.
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D000251:Adenosine Triphosphatases / Q000235:genetics; D000483:Alleles; D001426:Bacterial Proteins / Q000235:genetics*; D001564:Benzo(a)pyrene / Q000633:toxicity*; D045647:DNA Glycosylases; D004268:DNA-Binding Proteins / Q000235:genetics; D004259:DNA-Directed DNA Polymerase; D043382:DNA-Formamidopyrimidine Glycosylase; D004926:Escherichia coli / Q000201:enzymology* / Q000235:genetics; D029968:Escherichia coli Proteins; D009152:Mutagenicity Tests; D009153:Mutagens / Q000633:toxicity*; D009699:N-Glycosyl Hydrolases / Q000378:metabolism*; D018384:Oxidative Stress / Q000235:genetics; D010545:Peroxides / Q000494:pharmacology; D012097:Repressor Proteins / Q000235:genetics; D013014:SOS Response, Genetics; D014157:Transcription Factors / Q000235:genetics; D020122:tert-Butylhydroperoxide
D001426:Bacterial Proteins; D004268:DNA-Binding Proteins; D029968:Escherichia coli Proteins; D009153:Mutagens; D010545:Peroxides; D012097:Repressor Proteins; D014157:Transcription Factors; C499299:oxyR protein, E coli; D001564:Benzo(a)pyrene; D020122:tert-Butylhydroperoxide; D004259:DNA-Directed DNA Polymerase; C055218:UmuD protein, E coli; D045647:DNA Glycosylases; D009699:N-Glycosyl Hydrolases; C061738:mutY adenine glycosylase; D043382:DNA-Formamidopyrimidine Glycosylase; C468610:DNA-formamidopyrimidine glycosylase, E coli; C068631:UvrA protein, E coli; D000251:Adenosine Triphosphatases