ETHANOL-CONSUMPTION BY THE NURSING MOTHER INDUCES CYTOCHROME P-4502E1IN NEONATAL RAT-LIVER

Cytochrome P-4502E1 (P-4502E1) is not present in fetal rat liver becau se activation of the gene occurs shortly after birth. Ethanol is an in ducer of P-4502E1 in adult rats. Studies were carried out to evaluate whether transplacental induction of P-4502E1 by ethanol can occur afte r 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 ne onatal period by the mother was also determined. Pregnant rats receive d control or an ethanol-containing liquid diet starting on the 9th day of gestation and were killed on the 17th day or 21 st day of gestatio n 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 thi s model. Induction by ethanol of P-4502E1 protein and catalytic activi ty but not mRNA occurred in maternal liver. P-4502E1 mRNA, protein and catalytic activity were detected shortly after birth and increased ov er the 2-week neonatal period. The P-4502E1 content and oxidation of p -nitrophenol or dimethylnitrosamine by hepatic microsomes from neonate s of mothers consuming the ethanol diet were increased 2- to 3-fold co mpared with controls; however, P-4502E1 mRNA levels were not elevated. These results indicate that consumption of ethanol during the gestati onal and neonatal period can result in induction of P-4502E1 in hepati c microsomes of neonates, suggesting that the ethanol present in the m other'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 toxicolo gical significance to the newborn in view of the catalytic properties associated with P-4502E1.