EXPERIMENTAL-MODEL OF RENAL TUMORS IN POLYCYSTIC KIDNEYS - EFFECTS OFLONG-TERM 2-AMINO-4,5-DIPHENYLTHIAZOLE ADMINISTRATION IN RATS TREATEDWITH N-ETHYL-N-HYDROXYETHYLNITROSAMINE

We previously reported that treatment of Fischer-344 rats with 2-amino -4,5-diphenylthiazole (DPT) results in renal cystic changes. The prese nt study was undertaken to examine the effects of long-term DPT treatm ent after initiation of kidney carcinogenesis with N-ethyl-N-hydroxyet hylnitrosoamine (EHEN) in Wistar rats. One hundred forty-four 6-wk-old male Wistar rats were divided into 6 equal receiving groups: 1000 ppm EHEN or normal tap water for 2 wk followed by 1.06% DPT or basal diet for the subsequent 14 or 30 wk. Controls were maintained without trea tment throughout. Subgroups of 6 animals from each group were sacrific ed after 8, 16, 24, and 32 wk for histopathological assessment of lesi on development in the kidneys and liver. Animals treated with DPT firs t developed cystic changes of the kidneys (primarily at the corticomed ullary border) after 8 wk of treatment, and these changes progressed w ith time thereafter. In the groups in which DPT treatment was disconti nued after 14 wk, cysts then gradually decreased in size. All tumors d etected in the kidneys were histopathologically diagnosed as renal cel l adenomas. The tumor multiplicity after 32 wk of treatment was signif icantly higher in Group I, receiving EHEN + DPT for 30 wk (6.33 +/- 4. 36), and Group III, receiving EHEN + DPT for 14 wk (3.83 +/- 1.57), th an in Group V, EHEN alone (1.00 +/- 0.58) (p < 0.05). Renal cell tumor s within cysts were only seen in Groups I and III. The general bromode oxyuridine labeling indices for the kidneys at week 32 were significan tly higher in Group I (55.94 +/- 21.08 cells/mm(2)) and Group III (53. 75 +/- 12.38 cells/mm(2)) than in Group V (22.38 +/- 6.98 cells/mm(2)) (p < 0.05). In conclusion, DPT caused cystic changes in rat kidneys, which, however, gradually decreased in size after the treatment was di scontinued, suggesting a reversible nature. DPT clearly also promotes renal tumor development after EHEN initiation, and this effect persist s, to a certain extent, even after the insult is removed.