Reduced DNA damage induced in human melanoma cells by dacarbazine in the presence of deoxyribonucleosides.

Decarbazine induces DNA lesions in replicating DNA. We show here that deoxyribonucleosides, with the exception of thymidine, in doses of 250 microM or higher, prevent dacarbazine-induced DNA lesions. The DNA lesions that appear in the presence of thymidine can be prevented by aphidicolin, an inhibitor of DNA synthesis. Cytotoxicity analyses confirm that the combination thymidine-dacarbazine prevents cell outgrowth only partially, while other deoxyribonucleosides completely abolish the dacarbazine effect.