Razaka H, Salles B, Villani G, Johnson N P
Chem Biol Interact. 1986 Nov;60(2):207-15. doi: 10.1016/0009-2797(86)90029-3.
After exposure of bacteria to equal concentrations of cis-diamminedichloroplatinum(II) (DDP) and cis-diamminetetrachloroplatinum(IV) (DTP), the intracellular concentration of DTP was an order of magnitude greater than DDP. However, at identical intracellular drug concentrations, the Pt(IV) compound formed only half as many platinum-DNA lesions. For equal numbers of DNA lesions, the toxicity of both agents was identical whereas the mutagenicity of DTP was 7 times less than for DDP and its capacity to induce recA protein was less than DDP by a factor of 3.5. Bioreduction of Pt(IV) compounds to their corresponding Pt(II) analogues has been proposed as a mechanism for the reaction of Pt(IV) compounds with cellular DNA. According to this hypothesis, DTP would be reduced to DDP in the cell prior to its reaction with DNA and the platinum-DNA lesions of the two compounds should be identical. Our results suggest that reductive elimination can not entirely account for DNA damage caused by PT(IV) compounds in bacteria.
将细菌暴露于等浓度的顺二氯二氨铂（II）（DDP）和顺二氨四氯铂（IV）（DTP）后，DTP的细胞内浓度比DDP高一个数量级。然而，在相同的细胞内药物浓度下，Pt（IV）化合物形成的铂-DNA损伤只有DDP的一半。对于相同数量的DNA损伤，两种药物的毒性相同，而DTP的致突变性比DDP低7倍，其诱导recA蛋白的能力比DDP低3.5倍。有人提出将Pt（IV）化合物生物还原为其相应的Pt（II）类似物是Pt（IV）化合物与细胞DNA反应的一种机制。根据这一假设，DTP在与DNA反应之前会在细胞内还原为DDP，并且两种化合物的铂-DNA损伤应该是相同的。我们的结果表明，还原消除不能完全解释Pt（IV）化合物在细菌中引起的DNA损伤。
