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Reduced DNA Damage Induced in Human Melanoma Cells by Dacarbazine in the Presence of Deoxyribonucleosides¹

Radiumhemmet, Karolinska Hospital [U. L., S. L., U. N., G. W.], and Department of Histology, Karolinska Institutet [U. L., S. L.], S-104 01 Stockholm, Sweden

Decarbazine induces DNA lesions in replicating DNA. We show here that deoxyribonucleosides, with the exception of thymidine, in doses of 250 µM 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.

¹ This work was supported by grants from the Swedish Cancer Society and Karolinska Institutet.

² To whom requests for reprints should be addressed, at Radiumhemmet, Karolinska Hospital, PO Box 60500, S-104 01 Stockholm, Sweden.

Received 9/27/88. Revised 2/15/89. Accepted 2/16/89.