SUMMATION EFFECT OF N-BUTYL-N-(4-HYDROXYBUTYL)NITROSAMINE, N[4-(5-NITRO-2-FURYL)-2-THIAZOLYL]FORMAMIDE, N-2-FLUORENYLACETAMIDE, AND 3,3'-DICHLOROBENZIDINE ON URINARY-BLADDER CARCINOGENESIS IN RATS

Abstract

The effects of the sequential administration of 0.01% N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN), 0.15% N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide (FANFT), 0.025% N-2-fluorenylacetamide (2-FAA) and 0.3% 3,3''-dichlorobenzidine (3,3''-DCB) on urinary bladder carcinogenesis were examined in male Wistar rats. Each chemical was administered for 4 wk in various combinations. BBN for 4 wk resulted in no histopathological changes, mild diffuse cell growth and/or focal hyperplasia after 4, 8, 12 or 16 wk of observation. No bladder carcinomas were present in rats given only BBN or any 1 of the other 3 chemicals. Statistically significant incidences of bladder carcinomas occurred with the sequential administration of all 4 chemicals or the first 3 chemicals without 3,3''-DCB. Bladder cancer was also present in rats administered the sequence of FANFT, 2-FAA and 3,3''-DCB. No antagonistic effects between chemicals were observed.