Enhanced immunoreactivity of ras oncogene p21 protein in urinary bladder epithelium of rats treated with N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide.

Normal urothelium and various lesions of the rat urinary bladder induced by the dietary administration of 0.2% N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide (FANFT) (up to 77 weeks) or by the combination of 0.2% FANFT and the subsequent administration of 5% sodium saccharin or 2% DL-tryptophan (up to 104 weeks) were evaluated for immunoreactivity with monoclonal antibody to ras p21 by avidin-biotin immunohistochemistry. Seventy-one to 100% of transitional cell carcinomas showed strong reactivity to the antibody to ras p21 depending on treatment with long-term administration of FANFT or by 6 weeks administration of FANFT followed by sodium saccharin or DL-tryptophan. Focal reactivity to the ras p21 antibody was frequently observed in the hyperplastic (57-96%) or normal appearing urinary bladder epithelium (50-100%) in rats treated with FANFT (FANFT alone or in combination with sodium saccharin or tryptophan) but not in hyperplasia or normal epithelium in rats given sodium saccharin or tryptophan alone, without pretreatment with FANFT or in untreated controls. The present results show that there is a close association of enhanced immunoreactivity with ras p21 antibody in the urinary bladder epithelium to FANFT treatment, and that ras p21 is expressed in normal, hyperplastic and neoplastic lesions of the bladder of rats treated with FANFT. These results suggest that enhanced immunoreactivity with ras p21 is observed as a consequence of the treatment with FANFT but it alone does not reflect the progression from benign to malignant lesions.