Effect of cigarette smoke on hepatic and pulmonary cytochromes P450 in mouse: evidence for CYP2E1 induction in lung.
Pulmonary and liver microsomes of male NMRI mice were used to study the inductive effect of cigarette smoke on various cytochrome P450 isoforms implicated in precarcinogen and premutagen bioactivation. The enzymatic activities catalyzed by CYP1A1, CYP2B, CYP2C, CYP2D, CYP2E1 and CYP3A were induced in liver microsomes. Immunoquantification of lung and liver CYP1A1, 2E1 and 3A demonstrated that 1) CYP1A1 was induced in lung and liver, 2) CYP3A subfamily was induced in liver and not detected in lung, 3) CYP2E1 was slightly induced in liver whereas its pulmonary expression was more largely increased (6.8 fold) than CYP1A1 (2.0 fold). This latter data suggests that CYP2E1, which is known to be expressed in human lung, could actively participate in pulmonary carcinogenesis induced by cigarette smoke.
Villard
P H
PH
EA 859, Laboratoire de Pharmacocinétique et de Toxicologie, Faculté de Pharmacie, Marseille, France.
Seree
E
E
Lacarelle
B
B
Therene-Fenoglio
M C
MC
Barra
Y
Y
Attolini
L
L
Bruguerole
B
B
Durand
A
A
Catalin
J
J
D000818:Animals; D001711:Biotransformation; D015153:Blotting, Western; D002273:Carcinogens / Q000493:pharmacokinetics; D019392:Cytochrome P-450 CYP2E1; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis* / Q000378:metabolism; D015786:Cytochromes b5 / Q000378:metabolism; D004790:Enzyme Induction; D007527:Isoenzymes / Q000096:biosynthesis* / Q000378:metabolism; D008168:Lung / Q000201:enzymology*; D008297:Male; D051379:Mice; D008861:Microsomes / Q000201:enzymology*; D008862:Microsomes, Liver / Q000201:enzymology*; D010089:Oxidoreductases, N-Demethylating / Q000096:biosynthesis* / Q000378:metabolism; D010947:Plants, Toxic; D012906:Smoke / Q000009:adverse effects*; D014026:Nicotiana
D002273:Carcinogens; D007527:Isoenzymes; D012906:Smoke; D015786:Cytochromes b5; D003577:Cytochrome P-450 Enzyme System; D019392:Cytochrome P-450 CYP2E1; D010089:Oxidoreductases, N-Demethylating