The inorganic platinum compound cisplatin (CP) in Oncoplatin, an anticancer drug, as the test chemical and cyclophosphamide (CY) in Endoxan, another anticancer drug, as the positive control, were tested for their cytogenetic toxicity in bone marrow cells of Swiss mice. The end points selected were mitotic metaphase chromosomal aberration and mitotic index study at 24-hour post-treatment and micronucleus test at 30-hour post-treatment after a single intraperitoneal exposure. The doses of the chemicals tested were CP 2, 3 and 5 mg/kg and CY 40 mg/kg b.w. of mice. Each of the doses of CP induced a significant number of chromosomal aberrations, mostly chromatid breaks and fragments and a significant number of micronuclei. The mitotic index study indicated CP as nonmitotoxic. The female mice were found more sensitive to each of the doses of CP than the males by showing more chromosomal aberrations, a higher number of micronuclei and comparatively less percentages of dividing cells. CP was thus found to be highly clastogenic in bone marrow cells of Swiss mice.

Cisplatin (CP) (in Oncoplatin), a widely used drug in cancer chemotherapy, and cyclophosphamide (CY) (in Endoxan), another anticancer drug, were investigated as the test chemical and positive control, respectively, for their cytogenetic effects on spermatogonia of mice at 24 hours post-treatment after a single exposure. The different doses of the chemicals tested were CP 2, 3, 5 mg/kg and CY 40 mg/kg b.w. of mice. Each of the doses of CP induced a significant number of chromosomal aberrations, mostly chromatid breaks and fragments. The potential transmission of such cytogenetic effects of the chemicals from spermatogonia to spermatocytes was assessed at week 4 post-treatment from the primary spermatocytes, which showed a significant number of aberrant spermatocytes with atypical bivalents viz. spermatocytes with autosomal and/or XY univalents, tetravalents and with extra elements. The probable causes of the formation of univalents and tetravalents are discussed. The transmission of the cytogenetic effects of the chemicals from spermatogonia up to sperm was assessed at week 8 post-treatment from the morphology of sperm collected from vas. Quantitatively the transmission of such effects was found decreased substantially by the time the exposed spermatogonia became sperm. Still there was the occurrence of a few abnormal sperm at week 8 post-treatment. The probable causes of the quantitative decrease in the transmission of the effects from spermtogonia to sperm are discussed.

Possible protection from or potentiation of the cytogenetic toxic effects of cisplatin (CP) 5 mg/kg b.w. in mouse bone marrow, spermatogonia by three different doses of alpha-tocopheryl acetate (vitamin E) 100, 200 and 300 mg/kg, and the transmission of such effects in the male germline, were assessed. CP-induced chromosomal aberrations (CAs) in bone marrow were decreased in vitamin E pretreated mice, but significantly (P < or = 0.05) only with vitamin E 300 mg/kg. The percentages of dividing cells in bone marrow were increased in vitamin E-pretreated groups of mice, but not significantly. However, the frequency of CP-induced micronuclei (MN) in polychromatic erythrocytes (PCEs) declined significantly (P < or = 0.01) in all the vitamin E-pretreated groups of mice. In spermatogonia the CP-induced CAs were also decreased significantly by vitamin E 200 mg/kg (P < or = 0.01), and 100 and 300 mg/kg (P < or = 0.05). However, transmission of CP-induced cytogenetic toxic effects from spermatogonia to spermatocyte, resulting in the formation of aberrant primary spermatocytes, was enhanced significantly in the mice pretreated with vitamin E 100 mg/kg (P < or = 0.05) and 200 mg/kg (P < or = 0.01). But the enhancement in the transmission of such effects was not significant in the mice pretreated with vitamin E 300 mg/kg. Besides, there was no significant change in vitamin E-pretreated groups of mice in the transmission of cytogenetic toxicity of CP from spermatogonia to sperm with the manifestation of abnormal sperm morphology. Thus, vitamin E protected bone marrow and spermatogonia from the cytogenetic toxic effects of CP, particularly efficiently at the highest tested dose (300 mg/kg), but it failed to protect from the transmission of such effects in the male germline of mouse and rather potentiated them to some extent. Treatment with vitamin E, an antioxidant, might be capable of protecting noncancerous cells from the oxidative damage caused by cisplatin but it might also reduce the effects of cisplatin on cancerous cells. Thus, the benefits of antioxidant treatment during cancer chemotherapy is yet to be demonstrated clearly.

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