The Expression and Environmental Regulation of P450 Enzymes in Human Placenta

Abstract

The human placenta oxidizes several xenobiotics, although the spectrum of substrates and metabolic activities when compared with the liver appears somewhat restricted. Maternal cigarette smoking or PCB exposure increases the expression of CYP1A1. This induced activity is able to catalyze the activation of benzo(a)pyrene (B(a)P) into DNA-bound products, bothin vitro andin vivo. Studies on adult human liver bolster the concept that CYP1A1 and -1A2 are differentially expressed in hepatic and extrahepatic tissues. Studies with cDNA probe or enzyme specific antibodies and substrates forCYP2A, -2B, -2C, -2D, and-2E gene products have yielded negative results. There are only minimal activities that can be found in substantial quantities in placentas without maternal smoking; one example is 7-ethoxycoumarinO-deethylase (ECOD). Aromatase and cholesterol side-chain cleaving P450 mRNAs, proteins, and activities are measurable in human placentas and do not seem to be affected by maternal cigarette smoking.

Key Words:

• benzo(a)pyrene
• cytochrome P-450
• carcinogen-DNA adduct
• human fetus
• human liver
• monooxygenase