The formation of DNA cleaving species during the reduction of chromate by ascorbate.

da Cruz Fresco, P. and Kortenkamp, A. (1994) The formation of DNA cleaving species during the reduction of chromate by ascorbate. Carcinogenesis, 15 (9). pp. 1773-1778. 10.1093/carcin/15.9.1773 .

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DOI: 10.1093/carcin/15.9.1773

Abstract

A detailed study of the ability of chromate in combination with ascorbate to induce DNA single-strand breaks in the absence of iron(II) and copper(II) has been carried out. In solutions containing 1 mM ascorbate and chromate in the range 0.1-1 mM extensive DNA cleavage occurred. Chromate alone or the final product of the chromate/ascorbate reaction were not responsible for the cleavage observed. Evidence is presented that an intermediate generated during the reduction of chromate is the reactive species. No strand breaks occurred upon addition of catalase, pointing to a role for peroxidic species in the steps leading to the generation of the cleaving species. The exclusion of oxygen led to a substantial decrease in the number of strand breaks. Furthermore, the formation of strand breaks declined with decreasing concentrations of phosphate in the phosphate buffers used as the incubation medium. No DNA strand breaks were induced in medium containing HEPES. These observations rule out chromium(V) as the agent directly responsible for the DNA degradation, as chromium(V) is formed during the reduction of chromate by ascorbate in HEPES buffer. Our results lead us to suggest that the DNA-damaging ability of chromate upon reduction by ascorbate arises from the activation of oxygen exacerbated by phosphate and points to a peroxo or superoxo complex involving chromium(V) or chromium(IV) as a possible candidate.

Item Type:Article
Departments, units and centres:Department of Pharmacology > Centre for Toxicology
ID Code:2269
Journal or Publication Title:Carcinogenesis
Deposited By:Library Staff
Deposited On:23 Jun 2011 15:01
Last Modified:23 Jun 2011 15:01

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