MUTATIONS RECOVERED IN THE CHINESE-HAMSTER APRT GENE AFTER EXPOSURE TO CARBOPLATIN - A COMPARISON WITH CISPLATIN

Platinum-based compounds such as cisplatin and carboplatin are currently used for the treatment of a variety of solid tumors. Their primary mode of action involves the production of cross-links in DNA. These compounds induce mutations in bacterial as well as in mammalian cells. Previously we determined the sequence specificity and mutational outcome in the Chinese hamster aprt gene in mutants isolated after exposure to cisplatin. The second-generation platinum drug, carboplatin, is of clinical relevance because it displays different and less toxic effects. Here we report the mutagenic specificity of this related compound. Mutations recovered after exposure to carboplatin display the same preference for sequences that contain 5'-AGG-3', 5'-AGA-3' and 5'-GAG-3' as was found for cisplatin. We thus conclude that the mutagenic outcome of exposure to carboplatin and cisplatin respectively, is similar, if not identical.