We previously reported that treatment of Fischer-344 rats with
2-amino-4,5-diphenylthiazole (DPT) results in renal cystic changes. The present study was undertaken to examine the effects of long-term DPT treatment after initiation of kidney
carcinogenesis with N-ethyl-N-hydroxyethylnitrosoamine (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 treatment throughout. Subgroups of 6 animals from each group were sacrificed after 8, 16, 24, and 32 wk for histopathological assessment of lesion development in the kidneys and liver. Animals treated with DPT first developed cystic changes of the kidneys (primarily at the corticomedullary border) after 8 wk of treatment, and these changes progressed with time thereafter. In the groups in which DPT treatment was discontinued after 14 wk,
cysts then gradually decreased in size. All
tumors detected in the kidneys were histopathologically diagnosed as renal cell
adenomas. The
tumor multiplicity after 32 wk of treatment was significantly higher in Group I, receiving EHEN + DPT for 30 wk (6.33 +/- 4.46), and Group III, receiving EHEN + DPT for 14 wk (3.83 +/- 1.57), than in Group V, EHEN alone (1.00 +/- 0.58) (p < 0.05). Renal cell
tumors within
cysts were only seen in Groups I and III. The general
bromodeoxyuridine labeling indices for the kidneys at week 32 were significantly higher in Group I (55.94 +/- 21.08 cells/mm2) and Group III (53.75 +/- 12.38 cells/mm2) than in Group V (22.38 +/- 6.98 cells/mm2) (p < 0.05). In conclusion, DPT caused cystic changes in rat kidneys, which, however, gradually decreased in size after the treatment was discontinued, suggesting a reversible nature. DPT clearly also promotes renal
tumor development after EHEN initiation, and this effect persists, to a certain extent, even after the insult is removed.