Induction and time course of DNA single-strand breaks in lymphocytes from patients treated with dacarbazine.

Dacarbazine (DTIC) is an antitumor agent, used for the treatment of metastatic melanoma. It is metabolized to an alkylating agent which reacts with DNA. A fast and simple method was developed in order to measure drug-induced DNA damage in lymphocytes isolated from frozen blood samples of treated patients. The level of DNA damage was determined as single-strand breaks (SSB) by means of the alkaline elution technique using the fluorochrome Hoechst 33258. DTIC induced SSBs in lymphocytes. Most of the DNA damage was repaired after 20 h but after subsequent daily treatments there was an accumulation of SSB. The method described here can be used for monitoring DNA damage in lymphocytes of persons exposed to genotoxic compounds.