Casadevall M, Kortenkamp A
Department of Toxicology, School of Pharmacy, University of London, UK.
Carcinogenesis. 1994 Feb;15(2):407-9. doi: 10.1093/carcin/15.2.407.
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.
我们利用能在脱嘌呤/脱嘧啶位点（AP位点）切割DNA磷酸主链的试剂（腐胺、赖氨酸-色氨酸-赖氨酸和核酸外切酶III），获得了用铬酸盐和谷胱甘肽处理的分离DNA中诱导产生AP位点的证据。在谷胱甘肽（5 mM）存在的情况下，AP位点的水平随着铬酸盐浓度（75 - 200 microM）的增加而升高。单独的铬酸盐、谷胱甘肽，以及铬酸盐与谷胱甘肽反应的最终产物都不能诱导这种损伤。因此，还原过程中产生的中间物种似乎是造成损伤的原因。鉴于已知AP位点具有致突变性，我们的发现可能与铬酸盐致癌性所涉及的机制有一定关联。
