Effects of butylated hydroxyanisole pretreatment on low dose N-methyl-N'-nitro-N-nitrosoguanidine- or N,N-dibutylnitrosamine-induced rat forestomach or esophageal carcinogenesis.

The effects of butylated hydroxyanisole (BHA) pretreatment on subsequent low dose N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) or N,N-dibutylnitrosamine (DBN) treatment on forestomach or esophageal carcinogenesis were investigated in male F344 rats. Groups of animals were pretreated with 2% BHA or basal diet alone for 24 weeks and then were given 20 mg/kg body wt MNNG once every 2 weeks, 0.025% DBN in drinking water continuously or basal diet alone for the subsequent 24 weeks. Further groups of rats were similarly treated with BHA or basal diet alone for 24 weeks, placed on basal diet for the next 24 weeks and then treated with MNNG, DBN or basal diet alone for the subsequent 24 weeks. Animals were killed 48 or 72 weeks after the beginning of the experiment. Histopathological examination showed that the incidence of forestomach tumors was not significantly affected by the BHA pretreatment in the MNNG-treated groups. On the other hand, the incidence of esophageal squamous cell carcinomas was lower in the group pretreated with BHA followed by DBN than in that treated with basal diet followed by DBN (48 week experiment). There was no significant difference in esophageal tumor incidence in the 72 week experiment. The results thus indicate that continuous treatment with 2% BHA for 24 weeks does not exert initiating activity on forestomach and esophageal epithelia.