Hydrogen peroxide induces a specific DNA base change profile in the presence of the iron chelator 2,2' dipyridyl in Escherichia coli.
Pretreatment of Escherichia coli cultures with the iron chelator 2,2'-dipyridyl (1 mM) protects against the lethal effects of low concentrations of hydrogen peroxide (<15 mM). However, at H(2)O(2) concentrations equal to or greater than 15 mM, dipyridyl pretreatment increases lethality and mutagenesis, which is attributed to the formation of different types of DNA lesions. We show here that pretreatment with dipyridyl (1 mM) prior to challenge with high H(2)O(2) concentrations (>or=15 mM) induced mainly G:C-->A:T transitions (more than 100X with 15 mM and more than 250X with 20 mM over the spontaneous mutagenesis rate) in E. coli. In contrast, high H(2)O(2) concentrations in the absence of dipyridyl preferentially induced A:T-->T:A transversions (more than 1800X and more than 300X over spontaneous mutagenesis for 15 and 20 mM, respectively). We also show that in the fpg nth double mutant, the rpoB gene mutation (RifS-RifR) induced by 20 mM H(2)O(2) alone (20X higher) was increased in 20 mM H(2)O(2) and dipyridyl-treated cultures (110X higher), suggesting additional and/or different lesions in cells treated with H(2)O(2) under iron deprivation. It is suggested that, upon iron deprivation, cytosine may be the main damaged base and the origin of the pre-mutagenic lesions induced by H(2)O(2).
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Laboratório de Radiobiologia Molecular, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brasil.
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D015082:2,2'-Dipyridyl / Q000494:pharmacology*; D002614:Chelating Agents / Q000494:pharmacology*; D003596:Cytosine; D004249:DNA Damage; D004269:DNA, Bacterial / Q000187:drug effects*; D004926:Escherichia coli / Q000187:drug effects* / Q000235:genetics; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D008667:Metalloproteins; D009152:Mutagenicity Tests
D002614:Chelating Agents; D004269:DNA, Bacterial; D008667:Metalloproteins; C016298:chelatin; D015082:2,2'-Dipyridyl; D003596:Cytosine; D006861:Hydrogen Peroxide