The use of protein adducts to investigate the disposition of reactive metabolites of benzene.
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 and metabolites (benzene oxide [BO], 1,2-benzoquinone [1,2-BQ], and 1,4-benzoquinone [1,4-BQ]) in F344 rats and B6C3F1 mice following a single oral dosage of [13C6]benzene and/or [14C]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 BO 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.
Rappaport
S M
SM
Department of Environmental Sciences and Engineering, University of North Carolina, Chapel Hill 27599-7400, USA. stephen_rappaport@unc.edu
McDonald
T A
TA
Yeowell-O'Connell
K
K
D000818:Animals; D001554:Benzene / Q000378:metabolism* / Q000633:toxicity*; D016227:Benzoquinones / Q000378:metabolism; D015415:Biomarkers; D001853:Bone Marrow / Q000187:drug effects / Q000378:metabolism; D003510:Cyclohexanes / Q000378:metabolism; D006454:Hemoglobins / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D011506:Proteins / Q000187:drug effects* / Q000378:metabolism*; D051381:Rats; D011916:Rats, Inbred F344; D013045:Species Specificity
D016227:Benzoquinones; D015415:Biomarkers; D003510:Cyclohexanes; D006454:Hemoglobins; D011506:Proteins; C004532:quinone; D001554:Benzene; C025225:2-benzoquinone; C023372:benzene oxide