The use of protein adducts to investigate the disposition of reactive metabolites of benzene
Journal Article
·
· Environmental Health Perspectives
- Univ. of North Carolina, Chapel Hill, NC (United States)
Benzene is metabolized to a number of electrophilic species that are capable of binding to both DNA and proteins. We used adducts of hemoglobin (Hb) and bone marrow proteins to study the disposition of three benzene metabolites (benzene oxide [BO], 1,2-benzoquinone [1,2-BQ], and 1,4-benzoquinone [1,4-BQ]) in F344 rats and B6C3F{sub 1} mice following a single oral dosage of [{sup 13}C{sub 6}]benzene and/or [{sup 14}C]benzene. Our assays focused upon cysteine adducts that accounted for 38 to 45% of protein binding to Hb and 63 to 81% of protein binding to bone marrow. Although both mice and rats showed dose-related increases in Hb and bone marrow protein adducts of BQ and of the two benzoquinones, large intertissue and interspecies differences were noted, suggesting different preferences in metabolic pathways. The highest levels of adducts in mice were of 1,4-BQ (10-27% of all cysteine adducts), while in rats, BO adducts predominated in Hb (73% of all cysteine adducts) and 1,2-BQ adducts predominated in the bone marrow (14% of all cysteine adducts). High background levels of 1,2-BQ and 1,4-BQ adducts were also detected in both species, indicating that the toxic effects of quinone metabolites may only be important at high levels of benzene exposure. 16 refs., 3 tabs.
- Sponsoring Organization:
- USDOE
- OSTI ID:
- 472165
- Report Number(s):
- CONF-9506288--
- Journal Information:
- Environmental Health Perspectives, Journal Name: Environmental Health Perspectives Journal Issue: Suppl.6 Vol. 104; ISSN 0091-6765; ISSN EVHPAZ
- Country of Publication:
- United States
- Language:
- English
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