0000000000470734
AUTHOR
H. J. Arens
Control of the mutagenicity of aromatic amines by protein kinases and phosphatases
The role of protein kinase C and protein phosphatases was examined in the control of mutagenic metabolites of aromatic amines. Various metabolic activating systems derived from rat liver were treated with: 12-O-tetradecanoylphorbol-13-acetate (TPA), a protein kinase C modulator; okadaic acid (OA), a potent inhibitor of serine/threonine protein phosphatases (PP1 and PP2A); and ortho-vanadate (OV), an inhibitor of tyrosine phosphatases. TPA used over a wide concentration range (10−9–10−6 M) did not affect the bacterial mutagenicity of the aromatic amines and of the aromatic amide investigated, 2-aminoanthracene, 2-aminofluorene and 2-acetylaminofluorene (2AAF). At the molecular level, TPA did…
Significance of Posttranslational Modification of Drug Metabolizing Enzymes by Phosphorylation for the Control of Carcinogenic Metabolites
The total activity of foreign compound metabolizing enzymes may change by altering the amount or the specific activity of the enzyme by induction or repression, or by activation or inhibition. The important contribution of enzyme induction is well known (Conney 1982, Oesch 1986, Nebert and Jones 1989). This is a relatively slow process which requires the biosynthesis of the enzyme protein. The possibility of a faster regulation of foreign compound metabolism by posttranslational modification by phosphorylation of an already preexisting protein molecule has only recently received attention. A central role in the metabolism of foreign compounds is played by the cytochrome P450-dependent monoo…