POTENTIATION OF CIS-DDP AND PYRIDOXAL EFFECT ON ISOLATED DNA DURING SIMULTANEOUS APPLICATION

Pyridoxal and cis-diamminedichloroplatinum (II) (cis-DDP) have a diffe rent mode of interaction with DNA. Cis-DDP caused extensive transformi ng inactivation of pBR322 DNA but did not form strand breaks in DNA mo lecules. On the other hand, pyridoxal formed frank strand breaks in th e DNA chains and decreased DNA transforming activity. A higher level o f DNA transforming inactivation was obtained during simultaneous appli cation of both compounds than would be an additive effect of these com pounds applied to DNA independently. This synergistic effect can be as cribed to the introduction of thermolabile sites by the combined actio n of cis-DDP and pyridoxal. These lesions were converted by heat-treat ment to DNA strand breaks and detected electrophoretically. Using two different methods, cis.DDP and pyridoxal during simultaneous applicati on, interacted with DNA with higher efficiency.