7-Ethoxycoumarin and 7-ethoxyresorufin O-deethylase in human foetal and adult liver: studies with monoclonal antibodies
Pacifici, G.M.; Park, S.S.; Gelboin, H.V.; Rane, A.
Pharmacology and Toxicology 63(1): 26-29
1988
ISSN/ISBN: 0901-9928 PMID: 3261011 Document Number: 311722
The 7-ethoxycoumarin and 7-ethoxyresorufin O-deethylase activities were investigated in the microsomal fractions from 5 human adult and 3 foetal livers and 5 human foetal adrenals. The enzyme activity expressed as pmol/min. per mg microsomal protein was higher with 7-ethoxyresorufin as substrate in all investigated specimens with average values (.+-. S.E.M.) of 74 .+-. 27, 13 .+-. 3 and 12 .+-. 1 in adult and foetal livers and foetal adrenals, respectively. Monoclonal antibodies raised against 3-methylchloranthrene or phenobarbital induced rat liver cytochrome P-450 were investigated with respect to their inhibiting effects on the rate of O-deethylation of both substrates in human adult liver. Only the monoclonal antibody against the 3-methycholanthrene induced cytochrome P-450 inhibited the O-deethylation of 7-ethoxyresorufin to 64 to 79 percent of control values. The other antibody had no effect on this or the other O-deethylase activity. Thus, the 7-ethoxyresorufin O-deethylase is partly catalyzed in human adult liver by a cytochrome with an epitope that is recognized by the monoclonal antibody against 3-methylcholanthrene induced rat liver cytochrome P-450. With foetal liver the low activity of the enzyme became unmeasurable in the presence of this antibody.