THE IN-VITRO MORE EFFICIENTLY REPAIRED CISPLATIN ADDUCT CIS-PTGG IS IN-VIVO A MORE MUTAGENIC LESION THAN THE RELATIVE SLOWLY REPAIRED CIS-PTGCG ADDUCT

The toxic effect and the mutagenicity of two differentially repaired s ite-specific cis-diamminedichloroplatinum(II) (ris-DDP) lesions were i nvestigated. Detailed analysis of the UvrABC-dependent repair of the t wo lesions in vitro showed a more efficient repair of the cis-Pt.GG ad duct compared to that of the cis-Pt.GCG adduct (Visse et al., 1994). F urthermore, previously, a dependency of cis-DDP mutagenesis on UvrA an d UvrB, but not on UvrC was found (Brouwer et al., 1988). To possibly relate survival and mutagenesis to repair, plasmids containing the sam e site-specific cis-DDP lesions as those that were used in the detaile d repair studies, were transformed into Escherichia coli. The results indicate that both lesions are very efficiently bypassed in vivo. Muta tion analysis was performed using a denaturing gradient gel electropho resis technique, which allows identification of mutations without prev ious selection. Although the cis-Pt.GG adduct is in vitro more efficie ntly repaired than the cis-Pt.GCG adduct, it appeared to be mon mutage nic. We present a model in which this result is related to the previou sly observed dependency of the mutagenicity of cis-DDP lesions on the Uvr A and B proteins.