Evaluation of the teratogenic activity of hycanthone in mice and rabbits.
Hycanthone has been tested for embryotoxic activity in mice and rabbits. Treatment of mice on days 6-11 of gestation produced little embryotoxicity at a dose of 12.5 mg/kg, but produced teratogenic effects at 25 mg/kg and induced almost complete intrauterine death at 50 mg/kg. Single injections on various days of gestation demonstrated that the mouse conceptus is most sensitive to hycanthone-induced teratogenesis on gestation days 6 and 7, at which time a high incidence of exencephaly and skeletal malformations was found. Hycanthone (50 mg/kg) given to pregnant mice on day 7 of gestation depressed DNA synthesis in embryonic tissue, an effect which was evident 30 minutes after drug treatment and which lasted at least 3 hours. Following a single injection of [3H-U]hycanthone into 7-day pregnant mice, radioactivity was rapidly cleared from the maternal plasma, having a half-life of 1-2 hours; higher levels of radioactivity were attained in the embryonic vesicles than in maternal plasma at all time intervals tested. Hycanthone also had embryotoxic activity in rabbits. A dose of 25 mg/kg increased the incidence of intrauterine death, and at 50 mg/kg both embryolethal and teratogenic effects were noted.
D000014:Abnormalities, Drug-Induced / Q000209:etiology; D000818:Animals; D010064:Embryo Implantation / Q000187:drug effects; D004622:Embryo, Mammalian / Q000378:metabolism; D005260:Female; D005313:Fetal Death / Q000139:chemically induced; D005865:Gestational Age; D006826:Hycanthone / Q000097:blood / Q000494:pharmacology*; D008431:Maternal-Fetal Exchange; D051379:Mice; D011247:Pregnancy; D013723:Teratogens; D013892:Thioxanthenes / Q000494:pharmacology*; D013936:Thymidine / Q000378:metabolism; D013997:Time Factors
D013723:Teratogens; D013892:Thioxanthenes; D006826:Hycanthone; D013936:Thymidine