Summation effect of N-butyl-n-(4-hydroxybutyl)nitrosamine, N-(4-(5-nitro-2-furyl)-2-thiazoly)formamide, N-2-fluoroenylacetamide, and 3,3'-dichlorobenzidine on urinary bladder carcinogenesis in rats.

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-thiazoly)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 weeks in various combinations. BBN for 4 weeks resulted in no histopathological changes, mild diffuse cell growth, and/or focal hyperplasia after 4, 8, 12, or 16 weeks of observation. No bladder carcinomas were present in rats given only BBN or any one 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.