Effects of albendazole and albendazole sulfoxide on cultures of differentiating rodent embryonic cells.
Micromass cell culture systems for rat embryo midbrain (CNS) and limb bud (LB) cells were employed to assess the in vitro developmental toxicity of the human and veterinary anthelmintic albendazole (ABZ) and its sulfoxide metabolite (SOABZ). ABZ is reported to be teratogenic in rats, and is extensively metabolized to the sulfoxide derivative. It has been postulated that SOABZ is the reactive metabolite responsible for albendazole's developmental toxicity and anthelmintic activity in vivo. Three parameters for assessing developmental toxicity were measured: cell growth, differentiation, and cytotoxicity. CNS and LB cultures were equivalent in their sensitivities to both ABZ and SOABZ. ABZ was approximately 50-fold more potent than SOABZ. Immunohistochemical determinations of tubulin organization revealed that both ABZ and its sulfoxide metabolite elicit an accumulation of cells in the mitotic phase of the cell cycle. Since ABZ is one of the most potent agents tested in the micromass system to date, this anthelmintic should be considered a potential developmental toxicant.
Whittaker
S G
SG
Department of Environmental Health, University of Washington, Seattle 98195.
Faustman
E M
EM
D015766:Albendazole / Q000031:analogs & derivatives* / Q000633:toxicity*; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D004622:Embryo, Mammalian / Q000166:cytology / Q000187:drug effects*; D005121:Extremities / Q000196:embryology; D005455:Fluorescent Antibody Technique; D007150:Immunohistochemistry; D008636:Mesencephalon / Q000166:cytology / Q000187:drug effects / Q000196:embryology; D008870:Microtubules / Q000187:drug effects / Q000378:metabolism; D009499:Neutral Red; D051381:Rats; D011919:Rats, Inbred Strains; D014404:Tubulin / Q000378:metabolism
D014404:Tubulin; D009499:Neutral Red; D015766:Albendazole; C027186:albendazole sulfoxide; D004121:Dimethyl Sulfoxide