Neonatal modulation of adult rat hepatic microsomal benzo[a]pyrene hydroxylase activities by aroclor 1254 or phenobarbital

The constitutive and Aroclor 1254‐in‐duced activities of hepatic microsomal benzo[a]‐pyrene hydroxylases in male and female rats were determined in animals from ages 11 to 120 days. In 11‐day‐old noninduced male rats, benzo[a]pyrenediones and 9‐hydroxybenzo[a]pyrene were the major microsomal metabolites; in 21‐day‐old males benzo[a]pyrene‐diones and benzo[a]pyrene‐9,10‐dihydrodiol were predominant. In 60‐ and 120‐day‐old animals 3‐hydroxybenzo[a]pyrene was the major microsomal metabolite. A similar trend was observed for the development of benzo[a]pyrene hydroxylase activities in female rats. With the exception of 4,5‐di‐hydrodiol formation, the highest induction of individual and total benzo[a]pyrene hydroxylase activities by Aroclor 1254 was observed in the 21‐day‐old immature male rats, in which there was a 330‐ and 4.5‐fold increase in the formation of 3‐hydroxybenzo[a]pyrene and quinone metabolites, respectively. The induction of benzo[a]pyrene total metabolite formation by Aroclor 1254 in female rats from 11 to 120 days of age was relatively constant (i.e., 13.3‐ to 10.1‐fold induction); however, the relative induction of the individual benzo[a]pyrene hydroxylases was highly variable. In a second set of experiments, male and female rats were neonatally exposed to phenobarbital (600 μmol/kg) or Aroclor 1254 (100 μmol/kg), and the effects of these xenobiotics on neonatal imprinting of hepatic microsomal benzo[a]pyrene hydroxylase activities were determined in the 120‐day‐old animals. Neonatal exposure to phenobarbital resulted in a decrease in the Aroclor 1254‐induced rates of formation of dihydrodiol and quinone benzo[a]pyrene metabolites in male rat microsomes, an increase in the rates formation of the 9,10‐ and 7,8‐dihydrodiols in Aroclor 1254‐induced female rat microsomes, and a decrease in the constitutive and Aroclor 1254‐induced 3‐ and 9‐hydroxylase activities in hepatic microsomes from either sex. Neonatal exposure to Aroclor 1254 (100 μmol/kg) resulted in significantly lower Aroclor 1254‐induced rates of formation of the 9,10‐, 4,5‐ and 7,8‐dihydrodiol, quinone, and 9‐hydroxybenzo[a]pyrene metabolites in 120‐day‐old male rat microsomes and significantly decreased rates of formation of the 4,5‐dihydrodiol and quinone benzo[a]pyrene metabolites in Aroclor 1254‐induced female rat hepatic microsomes. Only minor differences were observed in the constitutive benzo[a]pyrene hydroxylase activities in microsomes from male or female rats neonatally treated with either phenobarbital or Aroclor 1254. These results demonstrate that neonatal exposure to phenobarbital or Aroclor 1254 can alter the adult metabolism of xenobiotics such as benzo[a]pyrene.