Ethanol consumption by the nursing mother induces cytochrome P-4502E1 in neonatal rat liver

Cytochrome P-4502E1 (P-4502E1) is not present in fetal rat liver because activation of the gene occurs shortly after birth. Ethanol is an inducer of P-4502E1 in adult rats. Studies were carried out to evaluate whether transplacental induction of P-4502E1 by ethanol can occur after oral consumption of ethanol by the pregnant mother. Because ethanol can be excreted in breast milk, the possible induction of P-4502E1 in neonatal liver when ethanol was consumed during the gestational and neonatal period by the mother was also determined. Pregnant rats received control or an ethanol- containing liquid diet starting on the 9th day of gestation and were killed on the 17th day or 21st day of gestation or allowed to deliver. The rats continued on their respective diets for the first 2 weeks of the neonatal period. P-4502E1 messenger RNA (mRNA), protein or catalytic activity was not detectable in fetal liver and was not induced in the fetuses from the ethanol-consuming mothers. Transplacental induction of P-4502E1 by ethanol did not occur in this model. Induction by ethanol of P-4502E1 protein and catalytic activity but not mRNA occurred in maternal liver. P-4502E1 mRNA, protein and catalytic activity were detected shortly after birth and increased over the 2-week neonatal period. The P-4502E1 content and oxidation of p-nitrophenol or dimethylnitrosamine by hepatic microsomes from neonates of mothers consuming the ethanol diet were increased 2- to 3-fold compared with controls; however, P-4502E1 mRNA levels were not elevated. These results indicate that consumption of ethanol during the gestational and neonatal period can result in induction of P-4502E1 in hepatic microsomes of neonates, suggesting that the ethanol present in the mother's milk is transferred to the newborn and is capable of inducing the P-4502E1 by a post-transcriptional mechanism. Such a mechanism of induction, which can occur immediately after birth, may be of toxicological significance to the newborn in view of the catalytic properties associated with P-4502E1.