The enzyme system metabolizing polycyclic
hydrocarbons is present and inducible in many cells
grown in culture. This has enabled us to study the
mechanism of enzyme induction. These studies
indicate that the induction process requires continuous
protein synthesis and proceeds after a lag
of 35min. RNA synthesis, however, is required
only during an initial period of 30-60min. This
RNA synthesis can occur during a block of protein
synthesis. This requirement for early RNA synthesis
suggests an inducer-mediated alteration of
genetic expression.
Two forms of aryl hydrocarbon hydroxylases can
clearly be delineated by their sensitivity to inhibition
by 7,8-benzoflavone. 7,8-Benzoflavone is a
strong inhibitor of 3-methylcholanthrene-induced
liver aryl hydrocarbon hydroxylase (>80%). 7,8-
Benzoflavone does not inhibit control or phenobarbitone-induced
liver aryl hydrocarbon hydroxylase.
The aryl hydrocarbon hydroxylase of extrahepatic
tissues from both control and 3-methylcholanthrene-induced
rats is sensitive to 7,8-
benzoflavone inhibition. However, the aryl hydrocarbon
hydroxylase in extrahepatic tissues from
induced rats is consistently more sensitive to 7,8-
benzoflavone, indicating the presence of two forms
of aryl hydrocarbon hydroxylases in extrahepatic
tissues.