Developmental abnormalities induced by 5-fluorouracil [5-FU] in rats

ABSTRACT

5-Fluorouracil [5-FU] was intraperitonealy injected at different doses to rats from 9[th] through the 12[th] day of gestation for determination of the optimal teratogenic dose [OTD], maximal teratogenic dose [MTD] and minimal LD[100] [MLD[100]]. OTD of 5-FU at 9[th], 10[th], 11[th] and 12[th] day of gestation was 28, 21, 22 and 24 mg/kg, respectively, while those of MTD were 34, 28, 32 and 32 mg/kg, respectively. MLD[100] of 5-FU at 9[th], 10[th], 11[th], and 12[th] day of gestation was 40, 32, 38 and 38 mg/kg, respectively, Nine groups of 10 pregnant rats each were used for revealing the developmental abnormalities induced by 5-FU When injected intraperitonealy in 2 dose levels [therapeutic and its double] on days 9, 10, 11, and 12 of pregnancy. In rats receiving 5-FU in single doses of 13.5 and 27.0 mg/kg on days 9-12 of gestation, the numbers of dead and resorbed fetuses and the post-implantation losses were significantly increased. On day 10 of gestation, the fetus is most susceptible to malformations, after which the frequency decreases proportionally to time. These malformations included growth retardation, thymus aplasia, pulmonary hypoplasia, dilatation of renal pelvis and absence of genital tubercle. Other observed skeletal anomalies were incomplete ossification of skull bones and absence of caudal verebrae, sternebrae and digits