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Increased clinical applications of the anticancer drug etoposide (a non-intercalative epipodophyllotoxin derivative) and the frequent induction of a second malignancy, particularly leukaemia, in post-etoposide-treated cancer survivors warrant detailed genotoxicity testing of etoposide. The genotoxicity test results available on etoposide are either primarily in in vitro test systems or in lower organisms after treatment with unusually high doses, or after chronic exposures, having little extrapolative value to humans. Therefore, a cytogenetic risk assessment study on etoposide in mouse in vivo was undertaken after a low dose (in accordance with the human therapeutic dose) single exposure. The cytogenetic toxicity of etoposide was assessed from bone marrow of mouse at three separate endpoints: chromosomal aberration and mitotic index studies at 24 h post-treatment and the micronucleus test (MNT) at 30 h post-treatment. The flame drying technique using colchicine, hypotonic sodium citrate, methanol-glacial acetic acid and Giemsa was followed for the preparation of slides for the metaphase chromosomal aberration and mitotic index studies and a simple technique was followed for the MNT. Although induction of chromosomal aberrations, excluding gaps, per 100 metaphases by 10 and 15 mg kg(-1) etoposide was not significant statistically, 20 mg kg(-1) of etoposide induced a significantly higher number of chromosomal aberrations in female (P < or = 0.01) and male (P < or = 0.05) mice. There was no significant change in the induced percentages of dividing cells by any of the doses of etoposide tested. The micronucleus induction also was not significant statistically with the lowest dose but it was significant in female (P

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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 ≤ 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 ≤ 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.