Enhanced mutagenesis during post-treatment incubation of Escherichia coli treated with cis-diamminedichloroplatinum(II).

Wild-type Escherichia coli were treated with cis-dichlorodiammineplatinum(II) (DDP) and then kept in a non-dividing state for 4 h. This post-treatment incubation did not increase survival, excision of platinum-DNA lesions was not observed, and post-treatment exposure to thiourea had no effect on the toxicity of DDP. In contrast, the mutation frequency increased by a factor of 3 and reached a plateau after 3 h incubation at 37 degrees C. The quantity of DDP on the bacterial DNA remained constant during this time. Post-treatment exposure to thiourea (which is reported to react with monofunctional platinum-DNA adducts) inhibited but did not reverse the increased mutagenicity. These results may reflect the evolution of monofunctional platinum-DNA lesions into bifunctional mutagenic adducts during post-treatment incubation of bacteria which have been exposed to DDP.