Background: Dacarbazine is an antitumour drug used with considerable success in the chemotherapy of a number of human neoplasias, particularly advanced disseminated melanoma. Dacarbazine is mutagenic in prokaryotic 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 micronuclei with the CREST antikinetochore antibody technique. Cytogenetic analysis on blood samples collected just before and 2 hours after the therapy was carried out at 48, 72 and 96 hours following lymphocyte stimulation. Results: A significant increase in micronucleus frequency was found at both 72 and 96 hours after therapy. For the only two patients analysed after more than one cycle, a decrease in micronuclei was observed after the third and the fourth therapy. Moreover, the CREST antibody 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 chromosome fragments (CREST-) was not significantly increased after therapy, either at 72 or 96 hours after lymphocyte stimulation, we suppose that DTIC mainly acted as an aneugenic agent. Conclusions: The lack of a significant micronucleus increase at 48 hours could suggest that this culture time is too short for providing cultures with a sufficient large number of diving cells. In conclusion, our results have shown that dacarbazine induced chromosome loss in lymphocytes from patients treated with this drug.
|Number of pages||5|
|Issue number||3 B|
|Publication status||Published - May 1998|
ASJC Scopus subject areas
- Cancer Research