Induction of hepatic and renal P4502E1 of neonatal rats exposed translactationally to ethanol.
The effect of maternal ethanol intake during lactation on neonatal cytochrome P4502E1 was investigated in Sprague-Dawley rats. Dams were exposed to 15% (v/v) ethanol in drinking water from day 1 of lactation to 4, 7 or 14 days postpartum. Significant (P < 0.01) enhancement of both hepatic and renal N-nitrosodimethylamine (NDMA) demethylase, an activity of P4502E1, was observed in lactating mothers given ethanol in drinking water. Demethylase activity also significantly increased (P < 0.01) in the 7- and 14-day livers of both female and male pups and in the 7- and 14-day female and 14-day male kidneys exposed to ethanol through the transmammary route. Cytochrome P4502E1 protein content, assayed by immunoblotting, increased in the maternal liver and kidney of all groups consuming ethanol. Neonatal P4502E1 protein content increased in the 7- and 14-day livers of both sexes and 14-day female kidneys exposed translactationally to ethanol. No effect of ethanol on enzyme activity or protein content of P4502E1 was observed in the liver or kidney of 4-day-old neonates. These results demonstrate the translactational effect of ethanol on neonatal P4502E1 enzyme, which is involved in the metabolism of many low molecular weight xenobiotics, and indicate the possibility of alterations occurring in the kinetics of neonatal drug and xenobiotic metabolism and also in processes connected with perinatal carcinogenesis.
Chhabra
S K
SK
Perinatal Carcinogenesis Section, National Cancer Institute, Frederick Cancer Research and Development Center, MD, USA.
Perella
C
C
Anderson
L M
LM
D000428:Alcohol Drinking / Q000009:adverse effects; D000818:Animals; D000831:Animals, Newborn; D015153:Blotting, Western; D019392:Cytochrome P-450 CYP2E1; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis / Q000187:drug effects* / Q000378:metabolism; D000431:Ethanol / Q000633:toxicity*; D005260:Female; D007668:Kidney / Q000187:drug effects* / Q000201:enzymology; D007774:Lactation / Q000187:drug effects*; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D018811:Maternal Exposure / Q000009:adverse effects*; D010089:Oxidoreductases, N-Demethylating / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D000431:Ethanol; D003577:Cytochrome P-450 Enzyme System; D019392:Cytochrome P-450 CYP2E1; D010089:Oxidoreductases, N-Demethylating