Chung M K, Kim J C, Roh J K
Toxicology Research Center, Korea Research Institute of Chemical Technology, Daejeon.
Reprod Toxicol. 1995 Mar-Apr;9(2):159-64. doi: 10.1016/0890-6238(94)00066-2.
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.
DA - 125是一种新的蒽环类抗肿瘤抗生素，由阿霉素衍生而来。临床前研究表明，它可能比阿霉素具有更强的活性和更低的心脏毒性。在Sprague - Dawley大鼠中研究了DA - 125诱导胚胎毒性的可能性。120只已交配的SD大鼠（阴道灌洗中有精子 = 第0天）被分为三个治疗组和一个对照组。在妊娠第7天至第17天，对怀孕大鼠静脉注射DA - 125，剂量分别为0、0.1、0.3和1.0毫克/千克/天。所有母鼠在妊娠第20天进行剖腹产。在1毫克/千克/天的剂量下，观察到母鼠食物摄入量减少、体重减轻和脾脏重量下降。还发现吸收发生率增加和胎儿体重减轻。此外，各种类型的外部、内脏和骨骼畸形的发生率分别为11.9%、41.8%和14.5%。特征性畸形包括无脑儿、腹裂、唇裂、侧脑室和第三脑室扩张以及肋骨融合等。在0.1和0.3毫克/千克的剂量下没有母体毒性或胚胎毒性的迹象。结果表明，DA - 125在大鼠中以最低母体毒性剂量具有致畸性。
