Effects of fructose 6-phosphate and adenylates on the activities of rabbit liver fructose bisphosphatase and phosphofructokinase.

The kinetics of induction of cytosolic DT-diaphorase (NAD(P)H dehydrogenase-quinone, EC 1.6.99.2) by benzo(a)pyrene (BP) in the liver of the 8-day-old rat has been studied. After a lag phase of 8 h, DT-diaphorase reaches its maximum activity in three waves, with plateau levels of activity between 15–18, 26–36, and 40 h after administration of BP, at 4, 15, and 26 times the basal activity, respectively. A lower degree of induction of DT-diaphorase could be observed in the kidney cortex of the young rat and in the liver of the adult rat. No induction was observed in the fetal liver and in the adult kidney cortex. Lead acetate treatment of the adult rat resulted in induction of DT-diaphorase by BP in the liver and in the kidney cortex. Induction could not be observed in the regenerating liver of the adult rat. Experiments with picolinic acid (PA)—as a G₁ inhibitor—administered simultaneously or at different time intervals after BP administration resulted in an inhibition of induction, depending on the time of administration of picolinic acid. It is concluded that a mitotic cell cycle is necessary for DT-diaphorase induction by BP. Evidence is presented that BP acts in late G₁. The kinetics of induction of aryl hydrocarbon hydroxylase (AHH) by BP in liver microsomes of the 8-day-old rat has been compared with the induction of cytosolic DT-diaphorase. The effect of PA on the induction of AHH has also been studied. In view of the differences in kinetics of induction and in the effects of PA, it is concluded that the induction of AHH and that of DT-diaphorase are dissociated. AHH induction may take place in all hepatocytes, in contrast to DT-diaphorase induction.