Enhancement by cysteinyl thiols of acetyltransferase-mediated, but not of sulfotransferase-mediated, binding of a pyrolysate-derived N-hydroxyarylamine, 2-hydroxyamino-6-methyldipyrido[1,2-a:3',2'-d]imidazole, to DNA.

The effect of thiols on the activation of a pyrolysate-derived N-hydroxyarylamine, 2-hydroxyamino-6-methyldipyrido[1,2-a:3',2'-d]imidazole (N-hydroxy-Glu-P-1), was studied in vitro. In hepatic cytosol of rats, [3H]-N-hydroxy-Glu-P-1 bound covalently to calf thymus DNA in the presence of acetyl CoA or 3'-phosphoadenosine-5'-phosphosulfate (PAPS). The extent of the binding of N-hydroxy-Glu-P-1 in a PAPS-dependent system was decreased by the addition of 10 mM glutathione, N-acetyl-L-cysteine, 2-mercaptoethanol or dithiothreitol. However, acetyl CoA-dependent binding of N-hydroxy-Glu-P-1 was stimulated by the addition of 10 mM N-acetyl-L-cysteine (3 fold), L-cysteine (2 fold) or glutathione (1.2 fold), but not 10 mM 2-mercaptoethanol or L-methionine. After hydrolysis of the modified DNA, no difference was detected in the physicochemical properties of the nucleoside adduct formed in the acetyl CoA-supported system with and without thiols. These results indicate that thiols with a cysteine residue are able to affect the activation of carcinogenic heterocyclic arylamines selectively by the modulation of the acetyltransferase-mediated, but not the sulfotransferase-mediated, pathway.