Differential Effects of Carcinogens on Hepatic Cytosolic Cyclic AMP-dependent Protein Kinase Activity

Differential effects of epigenetic tumor promoters and a genotoxic carcinogen on hepatic cytosolic cyclic adenosine 3′,5′-monophosphate-dependent protein kinase (CAMP-PK) were studied in vitro, since this enzyme is one of the major mediators of cell membrane permeability. Mirex (dodecachlorooctahydro-1,3,4-metheno-2H-cyclobuto[cd]pentalene), like phorbol ester TPA (12-0-tetradecanoylphorbol-13-acetste), caused significant inhibition of cAMP-dependent protein kinase activity ratio, whereas DDT [p, p′-trichlorobis(p-chlorophenyl)ethane] produced concentration-dependent changes. Diethylnitrosamine (DEN) and phenobarbitol (PB), however, showed a significant enhancement of the activity ratio. Interestingly, combinations of mirex, DDT with PB or DEN resulted in the potentiation of CAMP-dependent protein kinase activity in contrast to their effects when used separately. The results suggest that the influences of mirex and TPA in vitro on CAMP-PK are different from those observed in other cell and intact animal systems.