Potentially deadly carcinogenic chromium redox cycle involving peroxochromium(IV) and glutathione.
Peroxochromium(IV) complexes are putative DNA-damaging and mutagenic agents in chromium(VI)-mediated carcinogenesis. The reaction between aquaethylenediaminebis(peroxo)chromium(IV) and glutathione at neutral pH exhibits a cyclic redox process displaying a persistent recycling of Cr(IV) and Cr(VI) with the intervention of chromium(V) intermediates. The coordination by a glutathione molecule triggers an autooxidation of the Cr(IV)-peroxo complex to Cr(VI) via an internal electron-transfer process followed by reduction to Cr(IV) via metastable chromium(V) intermediates. The cycle is repeated by the second peroxo species. The Cr(V) and -(IV) intermediates have been characterized as mono- and bisglutathionato complexes with or without a coordinated peroxo moiety. These intermediates are capable of damaging DNA, as evidenced by single strand breaks and DNA oxidation. The implication here is that the potential for a persistent, if not perpetual, deadly chromium carcinogenic cycle exists in the cellular milieu through the assistance of molecular oxygen and glutathione.
Marin
Roberto
R
Department of Biomedical Sciences, Ohio University, Athens, Ohio 45701, USA.
Ahuja
Yachna
Y
Bose
Rathindra N
RN
D002273:Carcinogens / Q000737:chemistry / Q000494:pharmacology; D002840:Chromates / Q000737:chemistry* / Q000494:pharmacology; D004247:DNA / Q000737:chemistry / Q000187:drug effects; D004249:DNA Damage; D005978:Glutathione / Q000737:chemistry* / Q000494:pharmacology; D009153:Mutagens / Q000737:chemistry / Q000494:pharmacology; D010084:Oxidation-Reduction / Q000187:drug effects
D002273:Carcinogens; D002840:Chromates; D009153:Mutagens; C106706:chromium(IV)-glutathione complex; C066097:chromium(V)-glutathione complex; D004247:DNA; D005978:Glutathione