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INTERACTION OF HALOACETONITRILES WITH GLUTATHIONE AND GLUTATHIONE-S-TRANSFERASE
Citation:
Lin, E. AND C. Guion. INTERACTION OF HALOACETONITRILES WITH GLUTATHIONE AND GLUTATHIONE-S-TRANSFERASE. U.S. Environmental Protection Agency, Washington, D.C., EPA/600/J-89/042 (NTIS PB90103615).
Description:
The interactions of reduced glutathione (GSH) with haloacetonitriles (HAH) were carried out under various conditions and the depletion of GSH was determined. Haloacetonitriles reacted directly with glutathione in the absence of tissue extracts. he reactivities of haloacetonitriles were dibromoacetonitrile (DBAN) > bromochloroacetonitrile(BCAN) >> trichloroacetonitrile (DCAN) ailedto react with glutathione either in the presence or absence of glutathione-S-transferases. n the presence of ytosolic protein, the depletion of GSH by MCANl was increased, but GSH depletion by DBAN and TCAN was not altered. n the presence ofmicrosomes and a NADPH regenerating system, the consumption of GSH by MCAN and DCAN was increased whereas GSH consumption by DBAN and TCAN was decreased, indicating the biotransformation of HAN to metabolites with different reactivitities towards GSH. n the presence of bovine serum albumin (BSA), the consumption of GSH by TCAN was decreased while no difference was observed in the depletion of GSH by DBAN. ll haloacetopnitriles inhibited glutathione-S-transferase activities in vitro. CAN was the most potent inhibitor, followed by DBAN, BCAN, MCAN and DCAN was the least reactive.Glutathione concentration and glutathione-S-transferase activities in the liver were measured 1, 3 and 18 hr following a single oral administration of haloacetonitriles to rats. GSH concentration was depleted by MCAN at 1 hr and 3 hr after dosing, and rebounded to control level at 18 hr. he three dihalogenated acetonitriles depleted GSH at 1 hr. had no significant effect at 3 hr and elevated GSH level at 18 hr. The GSH level was not affected by TCAN at 1 hr. and became elevated at both 3 and 18 hr. lutathione-S-transferase activities were inhibited significantly only by DBAN at 18 hr. ur results showed that both GSH and GSH-S-transferases appear to play important roles in the detoxification of the haloacetonitiles.