Chaube S, Swinyard C A
Anat Rec. 1976 Nov;186(3):461-9. doi: 10.1002/ar.1091860311.
Pregnant Wistar rats injected intraperitoneally on gestational day 12 with single doses (100-1,000 mg/kg) or 600 mg/kg of 4(5)-(3,3-dimethyl-1-triazeno) imidazole-4-carboxamide (dic) were autopsied on day 21 (100-1,000 mg/kg) or at 24-hour intervals on days 13-20 (600 mg/kg). Controls received CMC on the same schedule. All fetuses were weighed and examined for urogenital system (UGS) malformations. Those given 600 mg/kg were also studied histologically. DIC produced significant growth retardation at all doses on day 21 (18-72%). UGS malformations occurred in 27-67% of the fetuses at 200-400 mg/kg and in 100% of those given 600 mg/kg or more of DIC. Abnormalities included renal growth inhibition, fusion, ectopia, and ureteropelvic dilatation. At 600 mg/kg renal and body weights were reduced 40 and 55%, respectively. Ureteropelvic dilation was common, and cortical glomeruli, nephric collecting tubules, and papillae were retarded in development. The juxtamedullary glomeruli were well developed. Proximal nephric tubular mitotic activity was 85% greater than in control animals (day 17). On the basis of pertinent morphological and physiological data, it is postulated that the dilated upper urinary tracts represent functional hydronephrosis incident to severe renal retardation and its resultant compensatory response.
在妊娠第12天腹腔注射单剂量（100 - 1000毫克/千克）或600毫克/千克的4(5)-(3,3 - 二甲基 - 1 - 三氮烯)咪唑 - 4 - 甲酰胺（DIC）的怀孕Wistar大鼠，在第21天（100 - 1000毫克/千克剂量组）或在第13 - 20天每隔24小时（600毫克/千克剂量组）进行解剖。对照组按相同时间表给予羧甲基纤维素（CMC）。对所有胎儿进行称重，并检查泌尿生殖系统（UGS）畸形情况。给予600毫克/千克剂量的大鼠还进行了组织学研究。在第21天，所有剂量的DIC均导致显著的生长迟缓（18 - 72%）。在200 - 400毫克/千克剂量组，27 - 67%的胎儿出现UGS畸形，而给予600毫克/千克及以上DIC的胎儿中100%出现畸形。异常情况包括肾脏生长抑制、融合、异位以及肾盂输尿管扩张。在600毫克/千克剂量时，肾脏和体重分别降低了40%和55%。肾盂输尿管扩张很常见，皮质肾小球、肾集合小管和乳头发育迟缓。近髓肾小球发育良好。近端肾小管有丝分裂活性比对照动物（第17天）高85%。根据相关的形态学和生理学数据推测，扩张的上尿路代表了严重肾脏发育迟缓及其导致的代偿反应所引发的功能性肾积水。
