The reductive conversion of chromium(VI) by ascorbate gives rise to apurinic/apyrimidinic sites in isolated DNA

• Type: Article in International Scientific Journal
• Date: 1995

Authors

Da Cruz Fresco, P (Author) FFUP; Shacker, F (Author) Other; Kortenkamp, A (Author) Other

Journal

Title: Chemical Research in Toxicology

Vol. 8

ISSN: 0893-228X

Publisher: American Chemical Society

Indexing

ISI Web of Knowledge - 23 Citations

Scopus - 22 Citations

Scientific classification

FOS: Medical and Health sciences

Other information

Authenticus ID: P-005-6CM

Abstract (EN): The formation of apurinic/apyrimidinic sites (AP-sites) and single strand breaks (SSB) by chromate and ascorbate (AsA) in isolated DNA was investigated using a number of agents that cleave DNA at AP-sites (putrescine, exonuclease III, the tripeptide Lys-Trp-Lys, and an AP-endonuclease containing fraction isolated from human fibroblasts). Relative to the number of SSB caused by chromate and AsA alone, all these agents induced additional nicking, indicating the induction of AP-sites. Chromate/AsA-induced AP-sites contain aldehyde groups, as cleavage by putrescine could be prevented by treatment with borohydride which reduced the aldehyde. The time course for the formation of both DNA lesions was very similar, and there was a 1:1 ratio of the number of SSB to the number of AP-sites. The addition of catalase to incubation mixtures containing chromate/AsA led to an almost complete suppression of AP-sites and SSB. In systems containing lower concentrations of chromate/AsA, the exclusion of oxygen inhibited the formation of both lesions. It is suggested that AP-sites and SSB arise from attack by reactive species deriving from chromate/AsA on one single site at DNA, probably the sugar moiety. In view of the known mutagenicity of AP-sites, these results could aid an understanding of the mechanisms underlying chromium(VI) carcinogenicity. © 1995 American Chemical Society.

Language: English

Type (Professor's evaluation): Scientific