Abstract
Changes in the kidneys were studied histopathologically and biochemically in F344 rats treated for long periods with 2-amino-4, 5-diphenylthiazole (DPT), with and without prior application of the renal carcinogen N-ethyl-N-hydroxyethylnitrosamine (EHEN). Experiment I: A total of 45 male 6-week-old F344 rats were divided into two groups; one receiving DPT at 1.06% in the diet (n=30) and the other being untreated (n=15). The observation period was 52 weeks. DPT caused cystic changes in the corticomedullary border, which were seen from the 4th week, progressed with time. Urine osmolarity began to decrease from the 6th week, however no biochemical signs of renal failure were noted before the 32nd week. High-performance liquid chromatography (HPLC) revealed 6 fractions, representing metabolites of DPT, in urine from DPT-treated rats. Experiment II: A total of 132 male 6-week-old F344 rats were divided into four groups: Group 1 (2-weeks 1, 000 ppm EHEN treatment followed by 1.06% DPT treatment), Group 2 (1.06% DPT treatment), Group 3 (2-weeks 1, 000 ppm EHEN treatment), and Group 4 (untreated controls). They were observed for 60 weeks. Cystic changes in the kidneys, as seen in Experiment I, were noted in Groups 1 and 2. Preneoplastic changes were seen only in Group 1, at incidences of 20% and 75% at weeks 48 and 60, respectively. Adenomas were seen in Groups 1 and 3, at incidences of 20% and 0%, and 25% and 20% at weeks 48 and 60, respectively. A carcinoma was diagnosed in 1 (20%) of the 5 rats from Group 1 in the 48th week. These results suggest that the DPT-treated rat can serve as a valid experimental model of congenital cystic kidney disease and chronic renal failure, and that DPT may promote EHEN-induced renal carcinogenesis.
