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Micronucleus analysis in peripheral blood lymphocytes from melanoma patients treated with dacarbazine.

Abstract

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.

MATERIALS AND 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.

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Authors

, , , , , , , ,

Source

Anticancer research 18:3B pg 1967-71

MeSH

Adult
Aged
Antineoplastic Agents
Chromosome Deletion
Dacarbazine
Female
Humans
Lymphocytes
Male
Melanoma
Micronuclei, Chromosome-Defective
Middle Aged

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

9677451

Citation

TY - JOUR T1 - Micronucleus analysis in peripheral blood lymphocytes from melanoma patients treated with dacarbazine. AU - Miele,M, AU - Bonassi,S, AU - Bonatti,S, AU - Martini,E, AU - Miglio,L, AU - Ottaggio,L, AU - Queirolo,P, AU - Sertoli,M, AU - Abbondandolo,A, PY - 1998/7/25/pubmed PY - 1998/7/25/medline PY - 1998/7/25/entrez SP - 1967 EP - 71 JF - Anticancer research JO - Anticancer Res. VL - 18 IS - 3B N2 - 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. MATERIALS AND 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. SN - 0250-7005 UR - https://www.unboundmedicine.com/medline/citation/9677451/Micronucleus_analysis_in_peripheral_blood_lymphocytes_from_melanoma_patients_treated_with_dacarbazine_ L2 - http://toxnet.nlm.nih.gov/cgi-bin/sis/search/r?dbs+hsdb:@term+@rn+4342-03-4 ER -