Differential inhibition of aryl hydrocarbon hydroxylase in human foetal liver, adrenal gland and placenta*.

Abstract

Abstract It is known from experiments on rats and mice that control and polycyclic aromatic hydrocarbon‐induced activities of aryl hydrocarbon hydroxylase differ profoundly with regard to their inhibition by several compounds. In order to obtain information about the nature of the human enzyme system from different tissues, the inhibition of aryl hydrocarbon hydroxylase (AHH) by different compounds in the human foetal and adult liver, foetal adrenal gland, as well as the placenta was studied. Substantial AHH activity was present in all the livers and adrenal glands, but only in term placentas from smoking mothers. The placental AHH was inhibited by 7,8‐benzoflavone, but not appreciably by SKF 525 A, aminopyrine or metyrapone. On the other hand, the foetal liver AHH was inhibited by SKF 525A, aminopyrine and metyrapone, whereas 7,8‐benzoflavone apparently activated the enzyme. The adult human liver AHH resembled that of foetal liver. The foetal adrenal AHH displayed a pattern of inhibition differing from both the liver and the placenta. Maternal cigarette smoking did not have a substantial effect either on the enzyme activity or on the inhibitory properties. Foetal hepatic AHH resembled the enzyme from control‐rat liver and the placental AHH was similar to the enzyme from 3‐methylcholanthrene‐treated rat liver. The effect of 7,8‐benzoflavone on control rat liver AHH activity varied greatly from the prenatal to the adult period, whereas AHH activity in MC‐treated rat liver was always strongly inhibited by 7,8‐benzoflavone.