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

C. Timchalk

Department of Pharmacology and Toxicology Albany Medical College Albany, NY 12208

A. K. Charles

Department of Pharmacology and Toxicology Albany Medical College Albany, NY 12208

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.

International Journal of Toxicology, Vol. 5, No. 4, 267-273 (1986)
DOI: 10.3109/10915818609140751
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