title: Evaluation of teniposide (VM-26)-induced toxicity on mouse spermatogenesis by flow cytometry.
abstract: Alteration in the testicular weight and various germ cell populations was studied in male mice treated with different doses (0.05, 0.25, 0.5, 1.0 and 2.0 mg/kg b. wt.) of teniposide (VM-26) at various post-treatment time periods. Treatment of mice with different doses of teniposide did not significantly alter the testicular weights, irrespective of the drug dose used. Flow-cytometric analysis of germ cells of the untreated control mice testes revealed four distinct DNA peaks corresponding to elongated spermatids (HC), round spermatids (1C), spermatogonia and non-germ cells (2C) and primary spermatocytes (4C). The region between 2C and 4C peaks represents cells that are actively synthesizing DNA (S-phase cells). Treatment of mice with different doses of teniposide resulted in a significant depletion in the relative percentage of spermatogonia from day 2 to 35 post-treatment depending on the drug dose. DNA-synthesizing, i.e. S-phase, cells declined significantly at day 1 post-treatment and continued to decline up to day 70 post-treatment for all the drug doses studied, except 2 mg/kg drug dose at day 28 post-treatment. A significant decline in the relative percentage of primary spermatocytes (4C) was observed at day 7 that continued up to day 70 post-treatment depending on the drug dose. Round spermatids (1C) declined significantly at day 21 post-treatment after administration of 0.25--2.0 mg/kg VM-26. The relative percentage of elongated spermatids showed a significant decline at day 28 after 1 and 2 mg/kg drug treatment. These alterations in different germ-cell populations are reflected in the various germ-cell ratios. The 4C:2C ratio showed a significant decline at day 7 and 14 post-treatment after 1 and 2 mg/kg VM-26 treatment, while the 1C:2C ratio declined significantly at day 21 post-treatment in the mice treated with 0.5 and 2.0 mg/kg of VM-26. 4C:S-phase and 1C:4C ratios increased significantly from day 1 to 70 post-treatment, depending on the drug dose. Our study demonstrates that the treatment of mice with low doses of VM-26 exerts cytotoxic effects on various germ-cell populations.
authors.affiliation: Department of Radiobiology, Kasturba Medical College, Manipal-576 119, India.
authors.forename: P
authors.initials: P
authors.lastname: Jyothi
authors.forename: G C
authors.initials: GC
authors.lastname: Jagetia
authors.forename: H
authors.initials: H
authors.lastname: Krishnamurthy
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity*; D001835:Body Weight; D004171:Diploidy; D004305:Dose-Response Relationship, Drug; D004996:Ethidium; D005434:Flow Cytometry; D005456:Fluorescent Dyes; D007274:Injections, Intraperitoneal; D008297:Male; D051379:Mice; D009929:Organ Size; D013076:Sperm Count; D013091:Spermatogenesis / Q000187:drug effects*; D013094:Spermatozoa / Q000145:classification / Q000187:drug effects* / Q000473:pathology; D013713:Teniposide / Q000633:toxicity*; D013737:Testis / Q000187:drug effects / Q000473:pathology; D013997:Time Factors
chemical_list: D000970:Antineoplastic Agents; D005456:Fluorescent Dyes; D013713:Teniposide; D004996:Ethidium