Studies on the ontogeny of goat hepatic cytochrome P-450-associated O-dealkylase activities using monoclonal antibodies: comparison to adult lung activity.

Abstract

The P-450-associated O-dealkylase activity towards ethoxyresorufin (EROD) and pentoxyresorufin (PROD) was measured in liver microsomes from 1-day-, 1-week-, 4-week-, 6-week-old and adult goats in order to characterize the ontogeny of cytochrome P-450 in this species. The inhibition of these enzyme activities by monoclonal antibodies raised against 3-methyl-cholanthrene-induced (MAb 1-7-1) and phenobarbital-induced (MAb 2-66-3) rat hepatic cytochrome P-450 was used to measure the contribution of the MAb-defined, epitope-specific P-450 to the total activities during these ages of goat development. EROD activity was undetectable until the 1st week of life and increased more than 25-fold by 4 weeks of age. The inhibition of EROD by MAb 1-7-1 increased from 20% in 1-week-old to 70% in adult goats. PROD activity, however, was detectable in the 1-day-old and reached adult levels by 6 weeks of age. The maximal inhibition (40%) of PROD activity by MAb 2-66-3 was demonstrated in 1-day-old goats. The measurement of these enzyme activities and their inhibition by the monoclonal antibodies demonstrated major differences in the ontogeny of these P-450 isozymes in goats. On the other hand, adult goat lung lacked detectable PROD activity, while it expressed approximately one tenth of the EROD activity exhibited by the liver. Over 70% of this activity was inhibitable by MAb 1-7-1.