Shin In-Sik, Lee Jong-Chan, Kim Kang-Hyeon, Ahn Tai-Hwan, Bae Chun-Sik, Moon Changjong, Kim Sung-Ho, Shin Dong-Ho, Kim Jong-Choon
Animal Medical Center, College of Veterinary Medicine, Chonnam National University, Gwangju, 500-757 Korea.
Toxicol Res. 2008 Dec;24(4):263-271. doi: 10.5487/TR.2008.24.4.263. Epub 2008 Dec 1.
Recently we reported that 2-bromopropane (2-BP) has maternal toxicity, embryotoxicity, and teratogenicity in Sprague-Dawley rats. The aims of this study are to examine the potential effects of 2-BP administration on pregnant dams and embryo-fetal development, and to investigate the effects of metabolic activation induced by phenobarbital (PB) on developmental toxicities of 2-BP. Pregnant rats received 1000 mg/kg/day subcutaneous 2-BP injections on gestational days (GD) 6 through 10 (Group II and Group IIII) or 11 through 15 (Group IV). Pregnant rats in Group III received an intraperitoneal PB injection once daily at 80 mg/kg/day on GD 3 through 5 for induction of the liver metabolic enzyme system. Control rats received vehicle injections only on GD 6 through 15. All dams underwent caesarean sections on GD 20 and their fetuses were examined for external, visceral, and skeletal abnormalities. Significant adverse effects on pregnant dams and embryo-fetal development were observed in all the treatment groups, and the maternal and embryo-fetal effects of 2-BP observed in Group II were higher than those seen in Group IV. Conversely, maternal and embryo-fetal developmental toxicities observed in Group III were comparable to those seen in Group II. These results suggest that the potential effects of 2-BP on pregnant dams and embryo-fetal development are more likely in the first half of organogenesis (days 6~10 of pregnancy) than in the second half and that the metabolic activation induced by PB pre-treatment did not modify the developmental toxic effects of 2-BP in rats.
最近我们报道了2-溴丙烷（2-BP）在斯普拉格-道利大鼠中具有母体毒性、胚胎毒性和致畸性。本研究的目的是检查给予2-BP对妊娠母鼠和胚胎-胎儿发育的潜在影响，并研究苯巴比妥（PB）诱导的代谢活化对2-BP发育毒性的影响。妊娠大鼠在妊娠第6至10天（第二组和第三组）或第11至15天（第四组）接受皮下注射2-BP，剂量为1000mg/kg/天。第三组妊娠大鼠在妊娠第3至5天每天腹腔注射一次PB，剂量为80mg/kg/天，以诱导肝脏代谢酶系统。对照组大鼠仅在妊娠第6至15天接受溶剂注射。所有母鼠在妊娠第20天进行剖腹产，并检查其胎儿的外部、内脏和骨骼异常情况。在所有治疗组中均观察到对妊娠母鼠和胚胎-胎儿发育有显著的不良影响，第二组中观察到的2-BP对母体和胚胎-胎儿的影响高于第四组。相反，第三组中观察到的母体和胚胎-胎儿发育毒性与第二组相当。这些结果表明，2-BP对妊娠母鼠和胚胎-胎儿发育的潜在影响在器官发生的前半期（妊娠第6至10天）比后半期更可能出现，并且PB预处理诱导的代谢活化并未改变2-BP对大鼠的发育毒性作用。
