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. Copyright © 1990, Wiley Blackwell. All rights reserved