MICRONUCLEUS ANALYSIS IN PERIPHERAL-BLOOD LYMPHOCYTES FROM MELANOMA PATIENTS TREATED WITH DACARBAZINE

Background: Dacarbazine is an antitumour drug used with considerable s uccess in the chemotherapy of a number of human neoplasias, particular ly advanced disseminated melanoma. Dacarbazine is mutagenic in prokary otic and eukaryotic cells, but no effect in vivo have been evaluated. Materials and methods: Peripheral blood lymphocytes from patients with metastatic melanoma undergoing dacarbazine chemotherapy every 21 days for a total of 7 cycles, were analysed for the presence of micronucle i with the CREST antikinetochore antibody technique. Cytogenetic analy sis on blood samples collected just before and 2 hours after the thera py was carried out at 48, 72 and 96 hours following lymphocyte stimula tion. Results: A significant increase in micronucleus frequency was fo und at both 72 and 96 hours after therapy. For the only two patients a nalysed after more than one cycle, a decrease in micronuclei was obser ved after the third and the fourth therapy. Moreover, the CREST antibo dy technique showed that the frequency of micronuclei containing whole chromosomes (CREST+) was significantly higher after therapy at 72 and 96 hours. As the frequency of micronuclei containing acentric chromos ome fragments (CREST) was not significantly increased after therapy, e ither at 72 or 96 hours after lymphocyte stimulation, we suppose that DTIC mainly acted as an aneugenic agent. Conclusions: The lack of a si gnificant micronucleus increase at 48 hours could suggest that this cu lture time is too short for providing cultures with a sufficient large number of diving cells. In conclusion, our results have shown that da carbazine induced chromosome loss in lymphocytes from patients treated with this drug.