title: Vinblastine-induced cytogenotoxicity in spermatogonia and its transmission in the germline cells of Swiss mice.
abstract: Vinblastine, a cytotoxic anti-neoplastic drug and a known mitotic spindle inhibitor, has reportedly induced numerical and structural alterations in chromosome complements of treated animals. In the present study, cytogenotoxic effects of three different doses of vinblastine (0.5, 1.0, and 1.5 mg/kg body weight) were assessed from mouse spermatogonia at 24 hours after treatment after a single intraperitoneal exposure. The transmission potential of such effects in the male germline of mice was also assessed from primary spermatocytic chromosome analysis and sperm morphology assay at weeks 4 and 8 after treatments, respectively. Induction of statistically significant percentages of aberrant spermatogonial metaphases (P ≤ 0.01) and chromosomal aberrations (excluding gaps) (P ≤ 0.05) in vinblastine-treated mice indicated its clastogenicity. Induction of significant percentages of aberrant primary spermatocytes with atypical bivalents (P ≤ 0.01) and different categories of abnormal sperm, although not with significant variation in frequency, indicated the transmission of vinblastine-induced cytogenotoxic effects from spermatogonia to spermatocyte to sperm. We conclude that vinblastine is cytogenotoxic to mouse spermatogonia and that such induced effects are transmissible in the male germline cells of Swiss mice. Potential transmission of such cytogenotoxic effects, from cancer survivors of reproductive age with vinblastine pretreatment through gametes, is a serious concern.
authors.affiliation: Genetic Toxicology Laboratory, Department of Zoology, Berhampur University, Berhampur, Orissa, India.
authors.forename: Anil K
authors.initials: AK
authors.lastname: Palo
authors.forename: Rabi S
authors.initials: RS
authors.lastname: Pandit
authors.forename: Ramesh C
authors.initials: RC
authors.lastname: Choudhury
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000633:toxicity*; D002869:Chromosome Aberrations / Q000139:chemically induced*; D004305:Dose-Response Relationship, Drug; D007274:Injections, Intraperitoneal; D008297:Male; D008677:Metaphase; D051379:Mice; D009153:Mutagens / Q000633:toxicity*; D013090:Spermatocytes / Q000187:drug effects* / Q000648:ultrastructure; D013093:Spermatogonia / Q000187:drug effects* / Q000648:ultrastructure; D014747:Vinblastine / Q000633:toxicity*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D009153:Mutagens; D014747:Vinblastine