Teratogenic effects of DA-125, a new anthracycline anticancer agent, in rats

DA-125 is a new anthracycline antitumor antibiotic derived from adriamycin. Preclinical studies suggest that it may have greater activity and less cardiac toxicity than adriamycin. The potential of DA-125 to induce embryotoxicity was investigated in the Sprague-Dawley rat. One hundred twenty mated SD rats (sperm in vaginal lavage = day 0) were distributed among three treated groups and a control group. DA-125 was given at dose levels of 0, 0.1, 0.3, and 1.0 mg/kg/day administered intravenously to pregnant rats from days 7 to 17 of gestation. All dams were subjected to caesarean section on day 20 of gestation. At 1 mg/kg/day, reduced food intake, reduced body weight, and decreased spleen weight were observed in dams. An increase in the resorption rate and a reduction in the fetal weight were also found. In addition, various types of external, visceral, and skeletal malformations occurred at an incidence of 11.9, 41.8, and 14.5%, respectively. Characteristic malformations included exencephaly, gastroschisis, cleft lip, dilatation of lateral and third ventricles, and fused ribs, among others. There were no signs of maternal toxicity or embryotoxicity at 0.1 and 0.3 mg/kg. The results show that DA-125 is teratogenic at a minimally maternally toxic dose in rats.