Potential Transmission of the Cytogenetic Effects of Cisplatin in the Male Germline Cells of Swiss Mice

Abstract

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.

Studies on the Genotoxic Effects of Anticancer Drug Carboplatin inin vivoMouse

“…Induction of sex-linked recessive lethal mutation in male germ cells (Woodruf et al 1980) and clastogenicity in spermatocytes and spermatogonia (Brodberg et al 1983) in Drosophila melanogaster by cisplatin have been reported. Cisplatin induced significant aberrant spermatocytes, autosomal and sex chromosomal univalents, tetravalents etc., in male mice (Adler and el-Tarras 1990;Choudhury et al 2000). Platinum compounds also reduced the sperm motility in humans (Kesseru and Leon 1974).…”

Gonadal damage and options for fertility preservation in female and male cancer survivors

“…In studies in male mice, cisplatin induced chromosomal aberrations in spermatocytes, as well as differentiating spermatogonia immediately after the treatment. However, long after exposure, the transmission of such effects was found to have decreased substantially by the time the exposed spermatogonia matured [68].…”

Male infertility and urological tumors: Pathogenesis and therapeutical implications

“…Cisplatin causes DNA cross-linking, an effect that inhibits DNA repair and synthesis, particularly in neoplastic cells. 48 Etoposide interferes with the transcription and replication of DNA which is followed by a cytotoxic effect. Bleomycin is an antibiotic agent capable of disrupting DNA chains in cancer cells.…”