Temporal changes in P-450 2E1 expression with continued ethylbenzene exposure.
The goal of this study was to examine the effect of duration of ethylbenzene exposure on cytochrome P-450-dependent activities. Male rats were treated with ethylbenzene by intraperitoneal injection for either 1 or 3 days, and microsomal preparations were examined for changes in the microsomal proteins and activities as well as the expression of specific P-450 isozymes. Two general patterns of induction were evident when different P-450-dependent activities were examined. (i) Cytochrome P-450 2B-dependent activities (e.g., p-nitroanisole demethylation, benzphetamine demethylation, and aromatic toluene hydroxylations) were induced both after 1 and 3 days of ethylbenzene exposure. (ii) Cytochrome P-450 2E1-dependent activities (e.g., N,N-dimethylnitrosamine demethylation and aniline hydroxylation) were induced after treatment with ethylbenzene for one day; however, after 3 days of ethylbenzene treatment these activities returned to control levels. Changes in these activities were consistent with changes in the levels of specific P-450 isozymes as determined by immunoblotting. Cytochrome P-450 2B levels were increased and P-450 2C11 levels were suppressed at both 1 and 3 days of ethylbenzene exposure. A temporal response in P-450 2E1 expression was observed, with P-450 2E1 levels increasing after a single ethylbenzene injection and returning to controls after administration of the hydrocarbon for 3 days. Rats were also subjected to a pair-feeding regimen to determine whether these effects were related to altered dietary status in ethylbenzene-treated rats. Neither P-450-dependent activities nor immunoreactive protein levels were altered in pair-fed rats. These results demonstrate that prolonging the duration of hydrocarbon exposure can produce differential effects on the expression of P-450 2E1, with levels being elevated after acute hydrocarbon administration, but not after more prolonged hydrocarbon exposure.
Sequeira
D J
DJ
Department of Pharmacology, Louisiana State, University Medical Center, New Orleans 70112.
Cawley
G F
GF
Eyer
C S
CS
Backes
W L
WL
D000814:Aniline Compounds / Q000378:metabolism; D000818:Animals; D000840:Anisoles / Q000378:metabolism; D001555:Benzene Derivatives / Q000008:administration & dosage / Q000494:pharmacology*; D019392:Cytochrome P-450 CYP2E1; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004128:Dimethylnitrosamine / Q000378:metabolism; D004435:Eating / Q000187:drug effects; D006900:Hydroxylation; D007527:Isoenzymes / Q000378:metabolism; D007700:Kinetics; D008297:Male; D008745:Methylation; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology*; D010089:Oxidoreductases, N-Demethylating / Q000378:metabolism*; D051381:Rats
D000814:Aniline Compounds; D000840:Anisoles; D001555:Benzene Derivatives; D007527:Isoenzymes; D003577:Cytochrome P-450 Enzyme System; D019392:Cytochrome P-450 CYP2E1; D010089:Oxidoreductases, N-Demethylating; C005306:4-nitroanisole; C004912:ethylbenzene; D004128:Dimethylnitrosamine; C023650:aniline