DEVELOPMENTAL TOXICITY AND TERATOGENICITY OF TRICHOSANTHIN, A RIBOSOME-INACTIVATING PROTEIN, IN MICE

The embryotoxic and teratogenic effects of trichosanthin (TCS), a protein isolated from tubers of Trichosanthes kirilowii (family Cucurbitaceae), were studied both in vivo and in vitro. The protein was administered i. p. to ICR mice on day 8. 0 of pregnancy, and the animals were sacrificed 1 day before parturition. The fetuses were fixed and subsequently sectioned. At the highest TCS dose employed (7.5 mg/kg body weight), the viability of fetuses declined to 70.2%, compared with 96.5% in the saline-treated control group. The number of resorbed fetuses increased, and the crown-rump length of the surviving fetuses was reduced. At the doses of 5.0 and 7.5 mg TCS/kg body weight, 2.3% and 9.0%, respectively, of die surviving fetuses were found to be abnormal. The abnormalities observed included exencephaly, micromelia, and short tail. When mouse embryos at the early organogenesis stage were cultured with TCS at a dose of 200 mug/ml or above, a significantly larger number of embryos were found to be abnormal as compared with the controls. The abnormalities were observed in the head, trunk, and limb regions. Hence, TCS produced adverse effects on prenatal development both in vivo and in vitro.