7-Alkoxyquinoline O-dealkylation by microsomes from human liver and placenta.
1. The O-dealkylation of seven 7-alkoxyquinoline derivatives by human hepatic and placental microsomes and the effect of maternal cigarette smoking on placental 7-alkoxyquinoline metabolism was studied. 2. None of several monoclonal antibodies to isoenzymes of cytochrome P450 had a clear effect on metabolism of the compounds by liver microsomes. 3. Maternal cigarette smoking induced the O-dealkylation of all of the 7-alkoxyquinoline derivatives, being greatest for 7-butoxy- and 7-benzyloxyquinoline. 4. Placental 7-alkoxyquinoline metabolism induced by smoking was partially inhibited by the monoclonal antibody 1-7-1 raised against 3-methylcholanthrene-induced rat liver P450. 5. None of the 7-alkoxyquinoline O-dealkylations could be assigned specifically to any known P450 isoenzyme in human liver or placenta.
Hakkola
J
J
Department of Pharmacology and Toxicology, University of Oulu, Finland.
Mäenpää
J
J
Mayer
R T
RT
Park
S S
SS
Gelboin
H V
HV
Pelkonen
O
O
D000818:Animals; D000911:Antibodies, Monoclonal; D001593:Benzyl Compounds / Q000378:metabolism; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D003640:Dealkylation; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008861:Microsomes / Q000201:enzymology / Q000378:metabolism*; D008862:Microsomes, Liver / Q000201:enzymology / Q000378:metabolism*; D010920:Placenta / Q000201:enzymology / Q000378:metabolism*; D011247:Pregnancy; D011804:Quinolines / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D012907:Smoking / Q000378:metabolism
D000911:Antibodies, Monoclonal; D001593:Benzyl Compounds; D065607:Cytochrome P-450 Enzyme Inhibitors; D011804:Quinolines; D003577:Cytochrome P-450 Enzyme System