Identification of N-acetyl-S-(2,5-dihydroxyphenyl)-L-cysteine as a urinary metabolite of benzene, phenol, and hydroquinone.
The metabolite 2-(S-glutathionyl)hydroquinone is formed when a microsomal incubation mixture containing either benzene or phenol is supplemented with glutathione. This metabolite is derived from the conjugation of benzoquinone, an oxidation product of hydroquinone. However, neither the glutathione conjugate or its mercapturate, N-acetyl-S-(2,5-dihydroxyphenyl)-L-cysteine, have been identified as metabolites resulting from in vivo metabolism of benzene, phenol, or hydroquinone. To determine if a hydroxylated mercapturate is produced in vivo, we treated male Sprague-Dawley rats with either benzene (600 mg/kg), phenol (75 mg/kg), or hydroquinone (75 mg/kg) and collected the urine for 24 hr. HPLC coupled with electrochemical detection confirmed the presence of a metabolite that was chromatographically and electrochemically identical to N-acetyl-S-(2,5-dihydroxyphenyl)-L-cysteine. The metabolite was isolated from the urine samples and treated with diazomethane to form the N-acetyl-S-(2,5-dimethoxyphenyl)-L-cysteine methyl ester derivative. The mass spectra obtained from these samples were identical to that of an authentic sample of the derivative. The results of these experiments indicate that benzene, phenol, and hydroquinone are metabolized in vivo to benzoquinone and excreted as the mercapturate, N-acetyl-S-(2,5-dihydroxyphenyl)-L-cysteine.
Nerland
D E
DE
Department of Pharmacology and Toxicology, University of Louisville, KY 40292.
Pierce
W M
WM
D000111:Acetylcysteine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism / Q000652:urine; D000818:Animals; D001554:Benzene / Q000378:metabolism*; D001711:Biotransformation; D002851:Chromatography, High Pressure Liquid; D004563:Electrochemistry; D008401:Gas Chromatography-Mass Spectrometry; D005978:Glutathione / Q000031:analogs & derivatives / Q000378:metabolism; D006873:Hydroquinones / Q000652:urine*; D008297:Male; D010636:Phenols / Q000652:urine*; D051381:Rats; D011919:Rats, Inbred Strains
D006873:Hydroquinones; D010636:Phenols; C067732:N-acetyl-S-(2,5-dihydroxyphenyl)cysteine; C040166:2-(S-glutathionyl)hydroquinone; D005978:Glutathione; D001554:Benzene; D000111:Acetylcysteine; C031927:hydroquinone