The generation of apurinic/apyrimidinic sites in isolated DNA during the reduction of chromate by glutathione.
We have obtained evidence for the induction of apurinic/apyrimidinic sites (AP-sites) in isolated DNA treated with chromate and glutathione using agents that cleave the DNA phosphate backbone at AP-sites (putrescine, Lys-Trp-Lys and exonuclease III). In the presence of glutathione (5 mM) the level of AP-sites rose with increasing concentrations of chromate (75-200 microM). Neither chromate nor glutathione alone nor the final product of the reaction between chromate and glutathione were capable of inducing the lesion. Thus, an intermediate species generated during the reduction process seems to be the cause of the damage. In view of the known mutagenicity of AP-sites our findings might be of some importance in relation to the mechanisms involved in chromate carcinogenicity.
Casadevall
M
M
Department of Toxicology, School of Pharmacy, University of London, UK.
Kortenkamp
A
A
D000595:Amino Acid Sequence; D002840:Chromates / Q000633:toxicity*; D004247:DNA / Q000187:drug effects*; D005978:Glutathione / Q000633:toxicity*; D008969:Molecular Sequence Data; D010084:Oxidation-Reduction; D011687:Purines / Q000378:metabolism*; D011743:Pyrimidines / Q000378:metabolism*
D002840:Chromates; D011687:Purines; D011743:Pyrimidines; D004247:DNA; D005978:Glutathione