2(3)-tert-Butyl-4-hydroxyanisole (2(3)-BHA) inhibits the action of a broad spectrum of carcinogens, mutagens and tumour promoters. This review discusses available information on four mechanisms by which 2(3)-BHA brings about these inhibitory effects. The first mechanism is induction of increased activities of enzyme systems having the capacity to detoxify carcinogenic compounds. The second is an alteration of the cytochrome P-450 system, resulting in metabolism of carcinogens to less carcinogenic metabolites. The third is the antioxidant effect of 2(3)-BHA. The fourth is poorly defined and relates to experiments in which 2(3)-BHA inhibits carcinogenesis when administered subsequent to the carcinogen.

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Studies related to the mechanism of 3-BHA-induced neoplasia of the rat forestomach.

The major objective of this investigation has been to determine the mechanism by which 3-BHA induces forestomach tumours in rodents. In vitro studies of liver microsomal metabolism of [14C]-3-BHA show binding of metabolites to microsomal protein which could be markedly decreased by addition of L-cysteine. p-Toluenesulphonic acid hydrolysis of the labelled microsomes showed a radioactive peak that co-chromatographed with the major product of the reaction of tert-butylquinone (tert-BuQ) and L-cysteine. In vivo binding of metabolites of [14C]-3-BHA to microsomal protein of the forestomach, glandular stomach and liver was determined. Forestomach microsomal protein contained 14 times as much bound radioactivity as glandular stomach and 12 times as much as liver. HPLC studies showed marked qualitative differences in the distribution of labelled compounds in hydrolysates of microsomes from the three tissues. The forestomach contained peaks not present in the other two tissues. In other studies it was shown that the 3-tert-butyl-5-methoxy-1,2-benzoquinone reacted rapidly with NADPH and NADH. tert-BuQ did so more slowly. Current data suggest that two factors may be of importance for 3-BHA carcinogenesis. The first is thiol depletion resulting from direct binding of quinone metabolites of 3-BHA to tissue thiols. Secondary reactions due to the presence of the quinones could also deplete -SH groups. Such thiol depletion could account for the threshold level existing for 3-BHA carcinogenesis. The second factor is an attack on tissue constituents from reactive metabolites of 3-BHA, as is evident from protein binding, and possibly also from oxygen radicals produced as a result of redox cycling of quinone and hydroquinone metabolites of 3-BHA.

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PubMedDate not supplied

The proliferative effect of dietary butylated hydroxyanisole on methylazoxymethanol treated colonic mucosa.

Pulse [3H]TdR labeling of CF1 mice fed butylated hydroxyanisole (BHA, 5 g/kg), given 6 injections of methylazoxymethanol (MAM), and examined 1 week later revealed reduction of colonic epithelial cell proliferation compared with rodents not fed BHA (labeling index (LI) 8.8 +/- 2.7 vs. 11.4 +/- 1.7). Dietary BHA did not prevent extension of the proliferative compartment to the upper third of crypts in MAM treated mice but did restrain the percentage of DNA synthesis shifted to the middle and upper third of the glands (18.5% vs. 26.4%). The mean distribution of the highest labeled cell in BHA was 12 cell positions below that seen in the MAM treated animals with no dietary BHA (position 14 vs. 26) indicating the ability of BHA to contain the size of the proliferative compartment. The accumulated differences between MAM treated groups based on LI along the entire length of the crypts revealed 85% greater activity in the mice not receiving BHA supplementation. Markedly reduced epithelial cell proliferation acts to interfere with the emergence of transmissable neoplastic mutations while containment of the proliferative compartment and restriction of the upward shift of DNA synthesizing cells inhibits adenomatous tumor formation known to appear in the upper regions of the crypts.

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PubMedDate not supplied

A histochemical study of hamster submandibular lesions.

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Animals↗

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Chemoprevention of pulmonary carcinogenesis by myo-inositol.

This abstract summarizes material presented at the "First International Symposium on Disease Prevention by IP6 and other Rice Components "held in Kyoto, Japan in June, 1998. The presentation deals primarily with studies of chemoprevention of pulmonary carcinogenesis by myo-inositol. This compound is largely formed by the dephosphorylation of inositol hexaphosphate (IP6, phytate) within the gastrointestinal tract in humans and animals. myo-Inositol is one of a relatively few compounds that has an inhibitory effect on carcinogenesis of the lung in experimental animals when administered during the post-initiation period. It prevents pulmonary adenoma formation in A/J mice when fed in the diet subsequent to administrations of benzo[a]pyrene or the tobacco specific carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) to the mice. A second compound, dexamethasone, also prevents pulmonary neoplasia under the same conditions. Experiments in which both myo-inositol and dexamethasone were administered together in the diet showed an additive inhibitory effect. The significance and utility of the chemopreventive properties of these agents remains to be determined.

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