Interaction of Platinum Compounds with the Genome: Correlation Between DNA Binding and Biological Effects

摘要

Evidence has been presented as to how cis-Pt binds to DNA and causes mutations and cell killing. Inhibition of DNA synthesis is thought to be the major reason why cells treated with cis-Pt die. Because cis-Pt binds to DNA in rat cells up to 10-fold more effectively than trans-Pt and since the cis isomer inhibits DNA synthesis 5-fold more effectively than the trans isomer, then from a simplistic point of view it is relatively easy to see how the cis isomer might be more toxic to an animal cell than the trans isomer. Furthermore, if inhibition of DNA synthesis initiates cell killing, then fast-growing tumor cells are more likely to be affected by Pt than normal nondividing cells. (ERA citation 04:052228)