Neovascularization in rats during urinary bladder carcinogenesis induced by N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide

Neovascularization in inbred F344 rats during urinary bladder carcinogenesis induced by N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide (FANFT) was examined by scanning electron microscopic observation of vascular casts. FANFT was fed to rats at a level of 0.2% of the diet for 6, 10, or 20 weeks, and vascular casts were examined in these rats at those times and after various times on control diets. Similar foci of vascular proliferation (types I and III) were observed after the use of FANFT as previously reported during bladder carcinogenesis induced by N-butyl-N-(4-hydroxybutyl)nitrosamine. However, the vascular proliferations were observed to regress as the FANFT-induced epithelial proliferations regressed, similar to the observation of reversible hyperplasias induced by cyclophosphamide or ulceration. Type I vascular foci were present after 6 and 10 weeks, but no vascular lesions were seen through week 20 after these groups of rats were fed the control diet for 4 or more weeks. The epithelial lesions present after 6 and 10 weeks of FANFT feeding also regressed and the mucosa returned to normal as observed by light microscopy. Type III foci were present after 12 weeks and were observed through week 20 when epithelial tumors appeared. Rats fed FANFT for 10 weeks and then the control diet developed hyperplastic epithelial lesions and carcinomas by week 52, whereas those fed FANFT for 6 weeks had normal bladders through 52 weeks.