The responses of hepatic and extrahepatic maternal and fetal tissues and placentas to the activating effects of hematin on cytochrome P-450-dependent monooxygenase (aryl hydrocarbon hydroxylase) activity were studied in two strains of mice. Tissues of a strain (C57BL/6J) that responds to the monooxygenase-inducing effects of 3-methyl- cholanthrene (3-MC) were compared with tissues of a non-responsive strain (DBA/2J) in order to determine whether hematin activation may play a role in the observed increases in extrahepatic monooxygenase activity following preexposure of pregnant animals to inducing agents. Maternal and fetal hepatic preparations from both strains of control mice exhibited decreased activity upon addition of hematin to reaction vessels. Monooxygenase activities in fetal hepatic preparations from both strains of 3-MC-pretreated mice also were decreased by hematin. Extrahepatic tissues of control C57BL/6J mice responded to the activating effects of hematin but the analogous tissues of 3-MC-pretreated mice of the same strain exhibited minimal or no significant response to hematin. The maternal brain tissue of DBA/2J mice exhibited a ninefold increase in monooxygenase activity upon addition of hematin in both the controls and 3-MC-pretreated mice. 3-MC-pretreatment of this strain resulted in abolition of hematin activation in fetal brain tissue but in the expression of statistically significant activation in placentas. Thus, no simple relationships between hematin activation and induction were evident, indicating that hematin activation is not responsible for the observation of increased enzymic activities in extrahepatic tissues after pretreatment with inducing agents.
We have reported2 an improved synthesis of 2-hydroxy-p-phenetidine. The N-acetyl derivative of this compound has recently been identified3 as a toxic metabolite of p-acetophenetide (phenacetin) in the urine of cats, dogs, and humans. Since the azomethine
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