The reductive conversion of the carcinogen chromium (VI) and its role in the formation of DNA lesions

• Type: Article in International Scientific Journal
• Date: 1996

Authors

Kortenkamp, A (Author) Other; Casadevall, M (Author) Other; Da Cruz Fresco, P (Author) FFUP

Journal

Title: Annals of Clinical and Laboratory Science

Vol. 26

Pages: 160-175

ISSN: 0091-7370

Publisher: Institute for Clinical Science

Indexing

ISI Web of Knowledge

Scopus - 25 Citations

Other information

Authenticus ID: P-00G-2Y9

Abstract (EN): The potential of Cr(VI), in combination with glutathione (GSH) or ascorbate (AsA) to induce apurinic/apyrimidinic sites (AP-sites) and single strand breaks (SSB) in isolated deoxyribonucleic acid (DNA) was investigated. The observation that both lesions were formed with equal probability and followed a similar time course suggests that they might arise from attack of a reactive species at C4' of the DNA sugar moeity. This idea is further substantiated by the finding that malondialdehyde-like products area released in chromate/GSH- and chromate/AsA-treated DNA. The generation of AP-sites and SSB was dependent on molecular oxygen and could be suppressed by the addition of catalase. Our results rule out hydroxyl radicals as the DNA damaging species. Furthermore, Cr(V), an intermediate formed during reaction with GSH or AsA, is not directly involved in the generation of DNA damage, unless activated by molecular oxygen. Our findings indicate that a superoxo- or peroxo-complex involving Cr(V) or Cr(IV) might be the species responsible for DNA damage. Evidence is presented that the DNA lesions arising from chromate/AsA have the potential to cause gene mutations.

Language: English

Type (Professor's evaluation): Scientific