Influence of long-term ethanol treatment on in vitro biotransformation of benzo(a)pyrene in microsomes of the liver, lung and small intestine from male and female rats.
The influence of long-term ethanol exposure of rats on the microsomal biotransformation of benzo(a)pyrene [B(a)P] was studied. Male and female Wistar rats received an increasing amount of ethanol in their drinking water: percentages rose to 15% (w/v) in 3 weeks. The ethanol content was kept at a concentration of 15% for another 3 weeks. Livers, lungs and intestinal epithelial cells of the rats were then isolated and microsomal fractions prepared. In all organs, the metabolite most formed was 3-hydroxy-B(a)P. In the liver, males showed significantly higher B(a)P hydroxylase activity than females. On the basis of experiments using monoclonal antibodies, a significant part of the B(a)P biotransformation in male rat liver microsomes can be attributed to the male specific P4502C11. In the lung and intestine, there were no significant differences between the sexes. In the liver, ethanol treatment significantly decreased the microsomal formation of phenolic metabolites. In microsomes of intestinal epithelial cells, ethanol treatment enhanced the formation of phenols and diols. In conclusion, ethanol consumption by rats in moderate amounts leads to an alteration in the microsomal biotransformation of B(a)P. Effects are most prominent in the liver, where the formation of phenols is significantly decreased.
van de Wiel
J A
JA
Department of Toxicology, Faculty of Medicine, University of Nijmegen, The Netherlands.
Meuwissen
M
M
Kooy
H
H
Fijneman
P H
PH
Noordhoek
J
J
Bos
R P
RP
D000818:Animals; D000911:Antibodies, Monoclonal; D001564:Benzo(a)pyrene / Q000378:metabolism*; D001711:Biotransformation / Q000187:drug effects; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000032:analysis; D000431:Ethanol / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D007421:Intestine, Small / Q000187:drug effects* / Q000378:metabolism; D007527:Isoenzymes / Q000032:analysis / Q000037:antagonists & inhibitors; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008168:Lung / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008861:Microsomes / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D000911:Antibodies, Monoclonal; D065607:Cytochrome P-450 Enzyme Inhibitors; D007527:Isoenzymes; D001564:Benzo(a)pyrene; D000431:Ethanol; D003577:Cytochrome P-450 Enzyme System