3,4‐Benzpyrene and N‐Methylaniline Metabolizing Enzymes in the Immature Human Foetus and Placenta*

The metabolism of 3,4‐benzpyrene (BP) and N‐methylaniline (MA) in several tissues of the immature human foetus and in the human placenta was studiedin vitro.The highest metabolizing activity of both substrates was detected in the liver. Compared to adult rat liver the range of hepatic metabolic activity varied from 5 to 10% for BP hydroxylase and from 5 to even 50% in some foetuses for MA demethylase. Adrenal gland homogenates had measurable BP and MA metabolizing activities. In the gastro‐intestinal tract, brain, kidneys and lungs there was only negligible activity or no activity at all. In one out of five placentas studied, enzyme activity comparable to that in the liver was detected. In foetal liver 12,000 × g supernatants, the Michaelis constants were 2.6 × 10‐5M for BP hydroxylase and 1.2 × 10‐4M for MA demethylase. The cofactor requirements of these enzymes suggested that they are drug metabolizing mixed‐function oxidases. Both enzymes were inhibitedin vitroby other compounds known to be substrates of liver microsomal drug metabolizing enzymes in a concentration range from 0.1 to 20 mM. The level of glucose‐6‐phosphate dehydrogenase activity in the foetal liver was found to be the same or even higher than in the adult rat or human liver.