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

Details

• Personal Author:
  Cha N ; Thompson DC ; Trush MA
• Description:
  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. [Description provided by NIOSH]
• Subjects:
  Energy Metabolism Enzymes Food Additives Neoplasms Occupational Health Safety
• Keywords:
  Cancer Enzyme-activity Food-additives In-vitro-studies Metabolic-study NIOSH-Grant NIOSH-Publication
• ISSN:
  0021-9258
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Journal Article
• Place as Subject:
  Maryland ; OSHA Region 3
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  264
• Issue:
  7
• NIOSHTIC Number:
  nn:00190468
• Citation:
  J Biol Chem 1989 Mar; 264(7):3957-3965
• Contact Point Address:
  Environmental Health Sciences Johns Hopkins University 615 N Wolfe Street Baltimore, MD 21205
• CAS Registry Number:
  2,6-Di-tert-butyl-4-methylphenol (CAS RN 128-37-0) ; tert-Butylhydroxyanisole (CAS RN 25013-16-5)
• Federal Fiscal Year:
  1989
• Performing Organization:
  Johns Hopkins University, Baltimore, Maryland
• Peer Reviewed:
  True
• Start Date:
  19830701
• Source Full Name:
  Journal of Biological Chemistry
• End Date:
  19850630
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:001f0a7956a9f60467bb5b36b046e4fcbc5ddb9e54c67b21f0d4f0391e09553db9df0b957cbe8cbf646c26ee9a4a918a65bfb54f4832803db44947868c661f07
• Download URL:
  https://stacks.cdc.gov/view/cdc/205757/cdc_205757_DS1.pdf
• File Type:
  [PDF - 943.16 KB ]