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KMID : 0379519910070020231
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한국독성학회지
1991 Volume.7 No. 2 p.231 ~ p.238
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BIOACTIVATION OF DIBROMOETHANE BY CONJUGATION WITH GLUTATHIONE
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Kim Dong-Hyun
F. Peter Guengerich
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Abstract
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The pesticide and carcinogen ethylene dibromide(EDB) is metabolized both by cytosolic GSH Stransferase 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 Stransferase action. The primary DNA adduct (?95) is S-[2 (N7-guanyl)ethyl] GSH and a minor adduct is S-[2-(N7guanyl)ethyl]cysteine, which is excreted in the urine and may serve as a biomarker of damage. In rat liver the level of the major DNA adduct is decreased by GSH depletion and elevated by either induction of GSH S-transferase or inhibition of the cytochrome P-450 oxidation of EDB by disulfiram. The unstable conjugate GS-CH2CH2CI and other cysteine or GSH derivatives have been synthesized and found to be a potent mutagen producing bacterial base pair mutation as does EDB.
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