Repeated oral benzene exposure alters enzymes involved in benzene metabolism.
Benzene is a known carcinogen and hematopoietic toxin in humans and experimental animals. The effect of acute, high-dose exposure to benzene on hepatic bioactivation and detoxication enzymes has been defined, while little is known about the effect of repeated, low-dose benzene exposure on these enzymes. Our objective was to determine whether repeated, oral benzene exposure alters enzymes involved in benzene metabolism. Specifically, we were concerned with cytochrome P-450-2E1, a bioactivation enzyme, and glutathione transferase and aldehyde dehydrogenase, two detoxifying enzymes. Female CD-1 mice were treated by gavage for 3 wk with benzene doses of 5 mg/kg (0.064 mmol/kg) or 50 mg/kg (0.646 mmol/kg) in corn oil. These doses of benzene produced 0.048 and 0.236 mumol muconic acid/d, respectively. We found that repeated exposure to 50 mg benzene/kg/d decreased P-450-2E1 activity by 34% and induced glutathione transferase activity by 30% without affecting aldehyde dehydrogenase activity. These changes in enzyme activities may serve a protective role against repeated exposure to benzene.
Daiker
D H
DH
Department of Pathology, University of Texas Medical Branch, Galveston 77555-0609, USA.
Moslen
M T
MT
Carr
J B
JB
Ward
J B
JB
D000284:Administration, Oral; D000444:Aldehyde Dehydrogenase / Q000187:drug effects*; D000818:Animals; D001554:Benzene / Q000008:administration & dosage / Q000378:metabolism / Q000633:toxicity*; D001835:Body Weight / Q000187:drug effects; D003577:Cytochrome P-450 Enzyme System / Q000187:drug effects*; D004790:Enzyme Induction; D005260:Female; D005982:Glutathione Transferase / Q000187:drug effects*; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D051379:Mice; D009929:Organ Size / Q000187:drug effects; D010634:Phenobarbital / Q000494:pharmacology; D013011:Sorbic Acid / Q000031:analogs & derivatives / Q000032:analysis
C005939:muconic acid; D003577:Cytochrome P-450 Enzyme System; D000444:Aldehyde Dehydrogenase; D005982:Glutathione Transferase; D001554:Benzene; D013011:Sorbic Acid; D010634:Phenobarbital