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Title: Butylated hydroxyanisole-induced alterations in cell kinetic parameters in rat forestomach in relation to its oxidative cytochrome P-450-mediated metabolism. Author: Verhagen H, Furnée C, Schutte B, Hermans RJ, Bosman FT, Blijham GH, ten Hoor F, Henderson PT, Kleinjans JC. Journal: Carcinogenesis; 1989 Oct; 10(10):1947-51. PubMed ID: 2791210. Abstract: Four groups of six male Wistar rats (85 +/- 7 g) were fed a diet containing 0% (control) or 2% of the carcinogenic food antioxidant butylated hydroxyanisole (BHA) for 2 weeks. In this experiment, feeding 2% BHA is equivalent to a dose of 2.1 +/- 0.3 g BHA/kg/day. One 0% BHA and one 2% BHA-fed group of rats were daily injected i.p. with the cytochrome P-450 inducer phenobarbital (PB; 60 mg/kg) in saline. These two groups were encoded 0PB and 2PB respectively. Simultaneously, two control groups of rats were injected i.p. with saline only (0 and 2 respectively). PB administration increased relative weight, cytochrome P-450 content and ethoxycoumarin-0-deethylase activity of livers as compared to control rats. In addition, cytochrome P-450-mediated oxidative demethylation of BHA into tert-butyl-hydroquinone (TBHQ), monitored as urinary TBHQ excretion, was significantly increased in PB-induced rats as compared to non-induced rats (0.59 +/- 0.19 versus 0.37 +/- 0.09%; P less than 0.05). The mean labelling index (LI) and potential doubling time (Tpot) in rat forestomach were significantly (P less than 0.01) altered in groups of rats fed 2% BHA as compared to their appropriate control groups. No differences in cell kinetic parameters between either the two control groups (0, 0PB) or between the 2% BHA-fed groups (2, 2PB) was observed. Thus, although an increase in oxidative demethylation of BHA as a response to PB administration is evident, biotransformation of BHA into TBHQ is not correlated to changes in cell kinetic parameters in rat forestomach. Moreover, in rats oxidative cytochrome P-450-mediated demethylation of BHA into TBHQ appears not to be related to the oral dose of BHA. This indicates that oxidative cytochrome P-450-mediated biotransformation of BHA does not contribute to the tumorigenicity of BHA in rat forestomach.[Abstract] [Full Text] [Related] [New Search]