EFFECT OF INDOMETHACIN ON [4-(5-NITRO-2-FURYL)-2-THIAZOLYL]FORMAMIDE-INDUCED URINARY-TRACT CARCINOGENESIS

The effects of indomethacin on the urinary bladder and renal pelvis in rats treated with N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide (FANFT ) were studied, Two hundred female Sprague-Dawley rats were divided in to four groups, Group 1 received control diet without added chemicals, Group 2 was treated with indomethacin (1 mg/kg per day) in the drinki ng water throughout the experiment, Groups 3 and 4 received 0.2% FANFT in the diet for seven weeks followed by control diet. In addition to FANFT, Group 4 received indomethacin, 1 mg/kg per day, for the entire experiment, The rats were sacrificed after 92 weeks. There were no uro thelial tumors in the control group, one renal pelvic tumor in the ind omethacin group, 4 tumors in the FANFT group and 10 urothelial tumors in the FANFT + indomethacin group. The difference between Groups 3 and 4 was statistically significant (P < 0.05), Moderate and severe hyper plasia of the renal pelvic and papillary epithelium was found in 15 of 48 rats in Group 2 (indomethacin only) as compared with 6 of 49 contr ol rats (P < 0.05). Moderate and severe hyperplasia was equally freque nt in Groups 3 and 4 (14 and 17 animals in each group, respectively), Twenty-four rats in Group 2 had mammary tumors as compared to 12 anima ls in Group 1 (P < 0.01), Five of the tumors in Group 2 were adenocarc inomas, There was no difference between the number of mammary tumors i n Groups 3 and 4 (36 and 32 animals in each group, respectively), The results suggest that indomethacin enhances FANFT-induced urinary tract carcinogenesis, Indomethacin also seems to exert some tumorigenic act ivity in the mammary gland.