CYP2E1 regulation by benzene and other small organic chemicals in rat liver and peripheral lymphocytes.
The inducibility of CYP2E1 was investigated in liver and peripheral lymphocytes of rats treated with benzene (0-10 mmol/kg body weight (bw), daily for 3 days, i.p., or 0 and 5 mmol/kg bw, daily for 14 days, i.p.) or toluene (0 and 5 mmol/kg bw, daily for 3 days, i.p.) and compared with that of pyridine (5 mmol/kg bw, i.p.) or acetone (5% in drinking water) both daily for 3 days. Acute benzene treatment (5 mmol/kg bw) increased both CYP2E1 apo-protein (2-fold) and p-nitrophenol hydroxylase (p-NPH) activity (1.4-fold) in liver, and CYP2E1 mRNA in both liver (2.2-fold) and peripheral lymphocytes (2.9-fold). The response to toluene was qualitatively similar, although smaller than that to benzene. As expected, acetone and pyridine treatments resulted in a 2- to 3-fold increase of p-NPH activity and CYP2E1 apo-protein content in liver, but not the mRNA levels. In addition, acute benzene and acetone treatments increased the 6-hydroxychlorzoxazone/chlorzoxazone metabolic ratio 1.6- and 3.1-fold, respectively. The subchronic treatment with benzene increased CYP2E1 mRNA and apo-protein from days 2 and 3 to day 14, respectively, whereas the enzyme activity increased transiently on days 3 and 5 only. These results show that acute/subacute benzene and acute toluene treatments induce CYP2E1 expression probably through a similar mechanism which might be different from that of pyridine or acetone, in that the former increase mRNA levels, both in liver and in peripheral lymphocytes, whereas the latter stabilized the apo-protein.
González-Jasso
Eva
E
Sección de Toxicología, Cinvestav-IPN, Mexico City D.F. 07360, Mexico.
López
Tomás
T
Lucas
Daniele
D
Berthou
Francois
F
Manno
Maurizio
M
Ortega
Arturo
A
Albores
Arnulfo
A
D000096:Acetone / Q000494:pharmacology; D000818:Animals; D001554:Benzene / Q000494:pharmacology*; D015153:Blotting, Western; D002469:Cell Separation; D002753:Chlorzoxazone / Q000031:analogs & derivatives* / Q000378:metabolism; D019392:Cytochrome P-450 CYP2E1 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D004790:Enzyme Induction / Q000187:drug effects; D015971:Gene Expression Regulation, Enzymologic; D066298:In Vitro Techniques; D007202:Indicators and Reagents; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008214:Lymphocytes / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology; D011725:Pyridines / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014050:Toluene / Q000494:pharmacology; D015430:Weight Gain / Q000187:drug effects
D007202:Indicators and Reagents; D011725:Pyridines; D012333:RNA, Messenger; D000096:Acetone; C039289:6-hydroxychlorzoxazone; D014050:Toluene; D019392:Cytochrome P-450 CYP2E1; D002753:Chlorzoxazone; D001554:Benzene; C023666:pyridine