TEMPERATURE-INDUCED INTERSTRAND CROSS-LINKS IN CISPLATIN-DNA ADDUCTS DETECTED BY ELECTROPHORESIS AND UV SPECTROPHOTOMETRY

Thermal melting profiles of DNA samples complexed with the anti-tumor drug cisplatin exhibit significant hypochromicity at pre-melting tempe ratures while a reduction in total hyperchromicity is observed in the melting region. Densitometric analysis of agarose gel electrophoresis pattern of DNA-cisplatin adducts heated to different temperatures in t he pre-melting region and frozen in their conformations reveals a grad ual retardation of mobility as the temperature increases. We attribute these results to a temperature induced transition in the mode of bind ing of cisplatin to DNA from an initial intrastrand monofunctional bin ding to bifunctional interstrand crosslink formation which results in gradual bending of the helix.