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The peroxidase-dependent activation of butylated hydroxyanisole and butylated hydroxytoluene (BHT) to reactive intermediates. Formation of BHT-quinone methide via a chemical-chemical interaction.

Thompson DC; Cha N; Trush MA

J Biol Chem 1989 Mar; 264(7):3957-3965

https://doi.org/10.1016/S0021-9258(19)84946-3

00190468

The metabolism and activation of butylated-hydroxyanisole (25013165) (BHA) and butylated-hydroxytoluene (128370) (BHT) were compared by two model peroxidase enzymes: horseradish-peroxidase and prostaglandin-H-synthase. Both horseradish-peroxidase and the peroxidase component of prostaglandin-H-synthase were able to oxidize BHA and BHT to reactive intermediates which could covalently bind to protein or form dimeric products. A chemical/chemical interaction was observed between BHA and BHT resulting in a significant stimulation of BHT oxidation and the formation of the potentially toxic butylated-hydroxytoluene-quinone-methide (BHT- quinone-methide). Three dimeric products of BHA were identified from a horseradish-peroxidase catalyzed reaction, whereas with prostaglandin-H-synthase only two dimers were found. Compared with BHA, BHT was a much poorer substrate for peroxidase as was evident from the finding that dimeric products were readily formed from BHA alone but not from BHT alone. BHA markedly stimulated, by 400 percent, the covalent binding of BHT and the formation of BHT- quinone-methide and stilbenequinone. A possible mechanism for the formation of BHT-quinone-methide and stilbenequinone from peroxidative reactions in the presence of both BHA and BHT was presented. In this scheme, when BHA was present in peroxidase incubations in the absence of BHT, BHA was metabolized to a reactive intermediate, phenoxyl radical, which subsequently dimerized or covalently bound to cellular macromolecules. In the presence of BHT, however, BHA was recycled back to the parent compound. Similarly, in the absence of BHA, BHT was metabolized to a reactive intermediate, phenoxyl radical, which was able to covalently bind to cellular macromolecules. A crucial point was the direct interaction of an oxidized metabolite of BHA with BHT.

NIOSH-Publication; NIOSH-Grant; Cancer; Food-additives; Metabolic-study; Enzyme-activity; In-vitro-studies

Environmental Health Sciences Johns Hopkins University 615 N Wolfe Street Baltimore, MD 21205

JBCHA3

25013-16-5; 128-37-0

19890305

Journal Article

36409

Grant

1989

Grant-Number-R03-OH-001833

7

0021-9258

Journal of Biological Chemistry

MD

Johns Hopkins University, Baltimore, Maryland