A TRANSPLACENTAL CARCINOGENICITY BIOASSAY IN CD-1 MICE WITH ZIDOVUDINE

In oral carcinogenicity bioassays, zidovudine (ZDV) induced vaginal ep ithelial cell tumors in mice given 30 or 40 mg/kg/day and rats given 3 00 mg/kg/day. To determine if lifetime exposure to ZDV, beginning peri natally, would alter this pattern of carcinogenicity, two groups of 60 pregnant CD-1 mice were given 20 or 40 mg/kg/day of ZDV in 0.5% methy l cellulose from Gestation Day 10 through Lactation Day 21, At weaning , 2 pups per sex from each of 35 litters in each group were assigned t o the study and given 20 or 40 mg/kg/day of ZDV in the drinking water until 17-35 days of age, followed by daily gavage for 24 months. Two a dditional groups of 60 pregnant CD-1 mice each were given 40 mg/kg/day of ZDV daily from Gestation Day 10 through Lactation Day 21; in one, ZDV treatment was halted at weaning and in the other, treatment was st opped 90 days after weaning. Two other groups of 60 pregnant CD-1 mice were left untreated (environmental control) or were given 0.5% methyl cellulose beginning on Gestation Day 10 (vehicle control). Vehicle co ntrol progeny received plain drinking water for 17-35 days postweaning and then 0.5% methyl cellulose daily by gavage for 24 months. ZDV tre atment did not affect survival or body weight in either sex. In female s given 20 or 40 mg/kg/day of ZDV for 24 months there was mild macrocy tic anemia, Similar, non-dose-related changes were seen in males in th ese groups, ZDV-related tumor findings were limited to the vagina, whe re there were 2 and 11 vaginal squamous cell carcinomas in mice given 20 or 40 mg/kg/day of ZDV daily, respectively. This incidence was not remarkably different from that seen in previously reported bioassays. It was perinatally, did not alter the previously reported pattern of c arcinogenicity and that under the conditions tested ZDV was not a tran splacental carcinogen. (C) 1997 Society of Toxicology.