Toxicological Research

Korean Society of Toxicology & Korea Environmental Mutagen Society (한국독성학회)
권호 표지

BIOACTIVATION OF DIBROMOETHANE BY CONJUGATION WITH GLUTAHIONE

  • Kim, Dong-Hyun (Dopin Control Center, Korean Advanced Institute of Science and Technology)
  • Published : 1991.12.01
Download PDF
⟨ Previous Next ⟩

Abstract

The pesticide and carcinogen ethylene dibromide(EDB) is metabolized both by cytosolic GSH S-transferase and by microsomal mixed function oxygenase. Cytochrome P-450 IIE1 appears to be major enzyme to metabolize EDB.EDB is activated to a mutagen by enzymatic conjugation with glutathione (GSH). Such activation is an exception to the general mode of detoxification via GSH S-transferase action. The primary DNA adduct (>95) is S-[2-(N7-guanyl)ethyl] GSH and a minor adduct is S-[2-(N7-guanyl)ethyl]cysteine, which is excreted in the urine and may serve as a biomarker of damage.

Keywords

References

  1. Cancer Res. v.50 Selectivity of rat and human glutathione S-transferases in activation of ethylene dibromide by glutathione conjugation and DNA binding and induction of unscheduled DNA synthesis in human hepatocytes Cmarik,J.L.;Inskeep,P.B.;Meredith,M.J.;Meyer,D.J.;Ketterer,B.;Guengerich,F.P.
  2. Toxicol. Appl. Pharmacol v.55 In vitro activation of 1,2-dichloroethane by microsomal and cytosolic enzymes Guengerich,F.P.;Crawford,W.M.Jr.;Domoradzki,J.Y.;Macdonald,T.L.;Watanabe,P.G.
  3. Chem. Res. Toxicol. v.4 Role of human cytochrome P-450 IIE1 in the oxidation of many low molecular weight cancer suspects Guengerich,F.P.;Kim,D.H.;Iwasaki,M.
  4. Biochemistry v.29 Comparison of the DNA alkylating properties and mutagenic responses of a series of S-(2-haloethyl)-substituted cysteine and glutathione derivatives Humphreys,W.G.;Kim,D.H.;Cmarik,J.L.;Shimada,T.;Guengerich,F.P.
  5. Cancer Res. v.49 Excretion of mercapturic acid S-[2-($N^7$-guanyl)ethyl]-N-acetylcysteine in urine following administration fo ethylene dibromide Kim,D.H.;Guengerich,F.P.
  6. Carcinogenesis v.11 Formation of the DNA adduct S-[2-($N^7$-guanyl)ethyl]glutathione from ethylene dibromide: effects of modulation of glutathione and glutathione S-transferase levels and lack of a role for sulfation Kim,D.H.;Guengerich,F.P.
  7. Chem. Res. Toxicol. v.3 Characterization of S-[2-($N^1$-adenyl)ethyl]glutathione as an adduct formed in RNA from 1,2-dibromoethane Kim,D.H.;Humphreys,W.G.;Guengerich,F.P.
  8. Biochemistry v.25 S-[2-($N^7$-guanyl)ethyl]glutathione, the major DNA adduct formed from 1,2-dibromoethane Koga,N.;Inskeep,P.B.;Harris,T.M.;Guengerich,F.P.
  9. J. Am. Med. Assoc. v.242 Two fetalities after acute occupational exposure to ethylene dibromide Litz,G.A.;Pond,S.M.;Osterlosh,J.D.;Wade,R.L.;Becker,C.E.
  10. Cancer Res. v.47 Search for ultimate chemical carcinogens and their reactions with cellular macromolecules Miller,E.C.;Miller,J.A.
  11. Br. J. Ind. Med. v.37 Motality experience of 161 employees ethylene to dibromide in two production unit Ott,M.G.;Scharnweber,H.C.;Langer,R.R.
  12. Proc. Natl. Acad. Sci.(U.S.A) v.80 Evidence for formation of an S-[2-($N^7$-guanyl)ethyl]glutathione adduct in glutathione-mediated binding of 1,2-dibromoethane to DNA Ozawa,N.;Guengerich,F.P.
  13. Toxicol. Appl. Pharmacol v.47 Carcinogenic Risk assessment: ethylene dibromide Ramsey,J.C.;Park,C.N.;Ott,M.G.;Gehring,P.J.
  14. Chem. Biol. Interact. v.20 The mutagenic effect of 1,2-dichloroethane on Salmonella typhimurium Rannug,U.;Sundvall,A.;Ramel,C.
  15. Cancer: A Comprehensive Treatise Weisburger,E.K.;Becker,F.F.(ed.)
  16. Pharmacol v.30 The influence of disulfiram and other inhibitors of oxidative metabolism on the formation of 2-hydroxyethyl-mercapturi acid from 1,2-dibromoethane by rat van Bladeren,P.J.;Hoogeterp,J.J.;Bremer,D.D.;van der Gen,A.
  17. Toxicol. Appl. Pharmacol. v.63 Carcinogenicity and toxicity of dibromoethane in the rat Wang,L.C.K.;Winston,J.M.;Hong,C.B.;Plotnick,H.