THE EXPRESSION AND ENVIRONMENTAL-REGULATION OF P450 ENZYMES IN HUMAN PLACENTA

The human placenta oxidizes several xenobiotics, although the spectrum of substrates and metabolic activities when compared with the liver a ppears 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 produ cts, both in vitro and in vivo. Studies on adult human liver bolster t he concept that CYP1A1 and -1A2 are differentially expressed in hepati c and extrahepatic tissues. Studies with cDNA probe or enzyme specific antibodies and substrates for CYP2A, -2B, 2C, -2D, and -2E gene produ cts have yielded negative results. There are only minimal activities t hat can be found in substantial quantities in placentas without matern al smoking; one example is 7-ethoxycoumarin O-deethylase (ECOD). Aroma tase and cholesterol side-chain cleaving P450 mRNAs, proteins, and act ivities are measurable in human placentas and do not seem to be affect ed by maternal cigarette smoking.