Urogenital anomalies in fetal rats produced by the anticancer agent 4(5)-(3,3-dimethyl-1-triazeno) imidazole-4-carboxamide

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.