Cytogenetic consequences of vinblastine treatment in mouse bone marrow

Background: Vinblastine (VBL), a vinca alkaloid, has very often been included in different cancer chemotherapeutic treatment regimens. Chemotherapy cures certain cancers and, at least, increases the life expectancy of cancer patients. However, in cancer survivors, a second malignancy frequently occurs after chemotherapy, which warrants detailed genotoxicity testing of the chemotherapeutic agents. The available genotoxicity test reports on VBL are self-contradictory and inconclusive. Thus, following a suitable experimental protocol, it is necessary to test the cytogenetic consequences of VBL treatment in mammals. Methods: Swiss mice received 1 of 3 different doses of VBL (0.5, 1.0 and 1.5 mg/kg body weight) as a single intraperitoneal injection. The cytogenetic toxicity of VBL was assessed from the induced aberrant metaphases, chromosomal aberrations (CAs) excluding gaps and the mitotic index (MI) 24 h after treatment, and micronuclei (MN) 30 h after treatment. Results: All 3 doses of VBL induced statistically significant (p less than or equal to 0.01) percentages of aberrant metaphases and CAs, but there was no significant change in the MI. The induced percentage of aberrant metaphases and CAs were decreased with the increase in the dose of VBL. On the other hand, there was a dose-dependent and significant (p less than or equal to 0.01) increase in MN induction. Conclusions: The results of this study indicate the clastogenic potential of VBL in the mouse bone marrow. In the present study, the induction of numerous relatively large-sized MN by VBL is in agreement with the reported aneugenic action of the drug. Although VBL is cytotoxic and is a spindle poison, the mechanism(s) involved in bringing about its clastogenic effects is yet to be elucidated. Copyright (C) 2004 S. Karger AG, Basel.