Skip directly to search Skip directly to A to Z list Skip directly to page options Skip directly to site content

NIOSHTIC-2 Publications Search

Search Results

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

Authors
Thompson-DC; Cha-N; Trush-MA
Source
J Biol Chem 1989 Mar; 264(7):3957-3965
NIOSHTIC No.
00190468
Abstract
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.
Keywords
NIOSH-Publication; NIOSH-Grant; Cancer; Food-additives; Metabolic-study; Enzyme-activity; In-vitro-studies
Contact
Environmental Health Sciences Johns Hopkins University 615 N Wolfe Street Baltimore, MD 21205
CODEN
JBCHA3
CAS No.
25013-16-5; 128-37-0
Publication Date
19890305
Document Type
Journal Article
Funding Amount
36409.00
Funding Type
Grant
Fiscal Year
1989
NTIS Accession No.
NTIS Price
Identifying No.
Grant-Number-R03-OH-01833
Issue of Publication
7
ISSN
0021-9258
Source Name
Journal of Biological Chemistry
State
MD
Performing Organization
Johns Hopkins University, Baltimore, Maryland
TOP