Micronucleus analysis in peripheral blood lymphocytes from melanoma patients treated with dacarbazine.
BACKGROUND
Dacarbazine is an antitumor 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.


METHODS
Peripheral blood lymphocytes from patients with metastatic melanoma undergoing dacarbazine chemotherapy every 21 days for a total of 7 cycles, were analyzed 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 analyzed 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.
Miele
M
M
CSTA-Mutagenesis, IST, Genoa, Italy.
Bonassi
S
S
Bonatti
S
S
Martini
E
E
Miglio
L
L
Ottaggio
L
L
Queirolo
P
P
Sertoli
M
M
Abbondandolo
A
A
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000633:toxicity*; D002872:Chromosome Deletion; D003606:Dacarbazine / Q000008:administration & dosage / Q000633:toxicity*; D005260:Female; D006801:Humans; D008214:Lymphocytes / Q000648:ultrastructure; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000235:genetics*; D048629:Micronuclei, Chromosome-Defective; D008875:Middle Aged
D000970:Antineoplastic Agents; D003606:Dacarbazine