Enhancement of N-[4-(5-Nitro-2-fury1)-2-thiazolyl]formamide-induced Carcinogenesis by Urinary Tract Infection in Rats

Epidemiological studies suggest that urinary tract infection is an important risk factor in the development of bladder cancer. Chronic urinary tract infection in rats is associated with urothelial hyperplasia and papillomatosis. In the Sprague-Dawley strain, exposure to the 5-nitrofuran, N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide (FANFT), is associated in particular with the development of renal pelvic tumors. The present study was designed to evaluate whether chronic urinary tract infection could enhance tumor development in FANFT-induced urinary tract carcinogenesis. One hundred forty-four female Sprague-Dawley rats were divided into the following groups. Group 1 received 0.2% FANFT in the diet for 7 wk followed by control diet. Group 2 received 0.2% FANFT in the diet for 7 wk followed by control diet. One wk after completion of FANFT administration, the suspension of 0.5 ml of Escherichia coli (06K13H1) was injected into the bladder through the urethra. Group 3 received 0.2% FANFT in the diet for 7 wk followed by control diet. One wk after completion of FANFT administration, a suspension of heat-killed E. coli (06K13H1) was injected into the bladder through the urethra. Group 4 received a suspension of 0.5 ml of E. coli (06K13H1) through the urethra and received control diet throughout the experiment. Group 5 was fed control diet only. The experiment continued for 104 wk. A significantly higher number of urinary tract tumors, particularly of the renal pelvis, was recorded in Group 2 compared to Groups 1, 3, 4, and 5. The majority of the rats in Groups 2 and 4 had morphological signs of urinary tract infections, particularly pyelitis and/or pyelonephritis. Thus, a single injection of E. coli (06K13H1) into the bladder results in an enhancement of FANFT-induced urinary tract carcinogenesis in the Sprague-Dawley rat, especially for renal pelvic tumors. The formation of dimethylnitrosamine or other nitroso compounds from nitrates in the urine or increased cell proliferation due to chronic inflammation or both may be important pathogenetic factors in the tumor development.