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1 Polish Journal of Environmental Studies

1 2006

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Expression of constitutive and inducible cytochromes P450 in fetal and newborn rat liver

100%

Czakaj P. , Wiaderkiewicz A. , Wiaderkiewicz R. , Palasz A.

nr 5

699-708

The developing organism lacks many of the cytochrome P450 isoforms detected in the adult, or they are expressed at very low levels. It remains controversial whether P450 gene regulatory mechanisms are present prenatally. As a result, the catalytic function of P450s in fetal tissues has been questioned. The aim of our study was to evaluate CYP: 1A1, 1A2, 2B1/2, 2E1, 3A1 and 3A2 expression in livers of 18- and 20-days-old fetuses, and newborns from untreated and P-naphthoflavone-, phenobarbital-, dexamethasone- or ethanol-treated Sprague-Dawley rats. CYP expressions were evaluated at both transcriptional (RT-PCR) and protein (Western blotting) levels. CYP mRNA expressions were detected on day 18 of gestation. CYP: 1A1, 2B1/2 and 3A1 proteins were found on day 18; CYP2E1 protein - on day 20; 1A2 and 3A2 protein - in newborn livers. Studied P450s demonstrated a very low expression in animal tissues before and just after birth but, in most cases, they were inducible. It is concluded that the inductory mechanisms of CYP: 1A1, 2B1/2, 3A1/2 and 2E1 but not CYP1A2, are functional in fetal liver at transcriptional or translational levels. The effects of metabolic activation of CYP1A2 substrates may be reduced in fetuses.