Abstract |
The stability of cysteinyl adducts of benzene oxide (BO) and mono-S-substituted cysteinyl adducts of 1,4-benzoquinone (1,4-BQ) was investigated in both hemoglobin (Hb) and albumin (Alb) following administration of a single oral dose of 400 mg [U-14C/13C6] benzene/kg body weight to F344 rats. Total radiobound adducts to Hb were stable, as were adducts formed by the reaction of [13C6]BO with cysteinyl residues on Hb. In both cases adduct stability was indicated by zero-order kinetics with decay rates consistent with the lifetime of rat erythrocytes. Hb adducts of 1,4-BQ were not detected, possibly due to the production of multi-S-substituted adducts within the erythrocyte. Regarding Alb binding, total radiobound adducts decayed more rapidly than expected (half-life of 0.4 days), suggesting that uncharacterized benzene metabolites were noncovalently bound or formed unstable adducts with Alb. Although adducts from reactions of BO and 1,4-BQ with Alb both decayed with rates consistent with those of Alb turnover in the rat, the half-life for 1,4-BQ-Alb (2.5 days) was shorter than that for BO-Alb (3.1 days), suggesting some instability of 1,4-BQ-Alb. Assuming similar rates of adduct instability in humans and rats, the 1,4-BQ-Alb adducts would be eliminated with a half-life of approximately 8 days, compared with BO-Alb, which would be expected to turnover with Alb (half-life of approximately 21 days).
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Authors | M A Troester, A B Lindstrom, L L Kupper, S Waidyanatha, S M Rappaport |
Journal | Toxicological sciences : an official journal of the Society of Toxicology
(Toxicol Sci)
Vol. 54
Issue 1
Pg. 88-94
(Mar 2000)
ISSN: 1096-6080 [Print] United States |
PMID | 10746935
(Publication Type: Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- Albumins
- Benzoquinones
- Carcinogens
- Cyclohexanes
- Hemoglobins
- quinone
- Benzene
- benzene oxide
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Topics |
- Albumins
(metabolism)
- Animals
- Benzene
(pharmacokinetics)
- Benzoquinones
(metabolism)
- Biotransformation
- Carcinogens
(pharmacokinetics)
- Cyclohexanes
(metabolism)
- Gas Chromatography-Mass Spectrometry
- Half-Life
- Hemoglobins
(metabolism)
- Male
- Protein Binding
- Rats
- Rats, Inbred F344
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