MODULATION OF N-BUTYL-N-(4-HYDROXYBUTYL) NITROSAMINE-INDUCED RAT URINARY BLADDER CARCINOGENESIS BY POST-TREATMENT WITH COMBINATIONS OF THREE PHENOLIC ANTIOXIDANTS

Abstract

The modifying activities of butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT) and tertiary butylhydroquinone (TBHQ) and of paired combinations of these compounds on urinary bladder carcinogenesis in male F344 rats pretreated with N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN) were investigated. Six weeks old animals were given 0.05% BBN in their drinking water for 4 weeks and then BHA, BHT or TBHQ, alone (0.8% each) or in pairs (0.4% each) in their diet for 32 weeks. Control rats received no further treatment after BBN administration. Surviving animals were killed at the end of week 36 of the experiment. The incidence of preneoplastic papillary or nodular hyperplasia (PN hyperplasia) was significantly higher in the group treated with BHA plus TBHQ after treatment with 0.05% BBN than in the group given the initiating carcinogen alone. The densities of PN hyperplasia (number per 10cm of basement membrane) were also significantly increased in all treated groups. However, no synergistic enhancing effects were observed. The incidences and densities of papillomas or carcinomas were not significantly different between any treated group or as compared to the controls. Thus the present experiments indicated that while BHA, BHT, and TBHQ all exerted enhancing effects in BBN-induced urinary bladder carcinogenesis in rats. no synergism regarding this promotion occurs, an important consideration for human risk assessment.