Effect of cigarette smoke on UDP-glucuronosyltransferase activity and cytochrome P450 content in liver, lung and kidney microsomes in mice.
The effect of cigarette smoke on the expression of several cytochromes P450 (CYP) and UDP-glucuronosyl-transferases (UGT) was studied in mice. The animals were exposed to cigarette smoke for 4 to 30 days. Enzymatic activities supported by CYP1A1, 1A2, 2B, 2E1 and the glucuronidation activity toward phenols were measured in lung, liver and kidney microsomes. Cigarette smoke induced several CYPs, especially in lung. CYP2E1 was more induced than CYP1A1 in this organ. The expression of CYP2E1 was also increased in kidney (5.6 times after 30 days). The glucuronidation in kidney was non-sensitive to the treatment whatever substrate used. In contrast, this activity was enhanced in liver and particularly in lung, in which the glucuronidation of 1-naphthol and 2-hydroxybiphenyl was increased by 122 and 180%, respectively. Interestingly, the times of induction differed according to the substrate used, thus suggesting the presence of different UGTs active toward phenols that were differentially affected by cigarette smoke. The UGT activities toward phenols were low in lung, when compared with those measured in liver or kidney. In conclusion, cigarette smoke greatly affected both glucuronidation activity and the hydroxylation reactions supported by CYPs in mouse liver and lung.
Villard
P H
PH
Laboratory of Toxicology (EA 2194), Mediterranean University, School of Pharmacy, Marseille, France.
Herber
R
R
Sérée
E M
EM
Attolini
L
L
Magdalou
J
J
Lacarelle
B
B
D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000032:analysis*; D015786:Cytochromes b5 / Q000032:analysis; D014453:Glucuronosyltransferase / Q000032:analysis*; D007668:Kidney / Q000187:drug effects* / Q000201:enzymology; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D008168:Lung / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D051379:Mice; D008861:Microsomes / Q000187:drug effects* / Q000201:enzymology; D014028:Tobacco Smoke Pollution / Q000009:adverse effects*
D014028:Tobacco Smoke Pollution; D015786:Cytochromes b5; D003577:Cytochrome P-450 Enzyme System; D014453:Glucuronosyltransferase