title: Microtubules of the mouse testis exhibit differential sensitivity to the microtubule disruptors Carbendazim and colchicine.
abstract: The testicular toxicant benomyl and its metabolite, carbendazim cause reproductive damage to the rat, an early sign of which is sloughing of germ cells with associated Sertoli cell fragments. However, the sensitivity of other mammalian species to these benzimidazole compounds is not clear. In this study, the effects of carbendazim and colchicine, a known microtubule disruptor, on the mouse seminiferous epithelium were characterized, and the amount of carbendazim reaching the mouse testis was measured. Testes were assessed for histological effects 3 h and 6 h after administration of carbendazim (2000 mg/kg, ip), and 6 h after intratesticular administration of either a low or high dose (5.3 or 117.6 micro g/g testis) of colchicine. Carbendazim caused no signs of histological damage to the mouse testis, and the microtubule cytoskeleton was intact and identical to controls based on immunostaining with tyrosinated alpha tubulin and beta tubulin antibodies. Similarly, the seminiferous epithelium of mouse testis was undamaged and the microtubule cytoskeleton was intact after a low dose of colchicine, while a comparable dose of colchicine injected into rat testis caused marked toxicity. However, mouse testes did show microtubule disruption and severe germ cell sloughing after administration of a high dose of colchicine. The amount of carbendazim measured in mouse testis was 375 nmol/g testis, which is higher than the value measured in rat testis after a toxic dose of carbendazim. Therefore, carbendazim reaches the mouse testis at or above levels measured in the rat, yet the mouse is apparently insensitive to this microtubule disrupting agent.
authors.affiliation: Department of Environmental Toxicology, University of California, One Shields Avenue, Davis, California 95616, USA. Imcorrea@ucdavis.edu
authors.forename: Liane M
authors.initials: LM
authors.lastname: Correa
authors.forename: Masaaki
authors.initials: M
authors.lastname: Nakai
authors.forename: Christina S
authors.initials: CS
authors.lastname: Strandgaard
authors.forename: Rex A
authors.initials: RA
authors.lastname: Hess
authors.forename: Marion G
authors.initials: MG
authors.lastname: Miller
mesh_terms: D000818:Animals; D001562:Benzimidazoles / Q000633:toxicity*; D002219:Carbamates; D003078:Colchicine / Q000633:toxicity*; D003599:Cytoskeleton / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008870:Microtubules / Q000187:drug effects / Q000473:pathology* / Q000648:ultrastructure; D012671:Seminiferous Tubules / Q000187:drug effects / Q000648:ultrastructure; D013737:Testis / Q000187:drug effects / Q000473:pathology* / Q000648:ultrastructure; D014404:Tubulin / Q000378:metabolism
chemical_list: D001562:Benzimidazoles; D002219:Carbamates; D014404:Tubulin; C006698:carbendazim; D003078:Colchicine