Inactivation of the Polymerase but not the DNA Binding Function of ADPRT by Destabilization of one of its Zn2+ Coordination Centers by 6-Nitroso-1,2-Benzopyrone

In the course of studies on the metabolism of inhibitors of poly (ADP- ribose) transferase (ADPRT), we observed that the inhibitor 6-amino-1,2-benzopyrone (6-ABP) (1) when metabolized by rat liver microsomal preparations is oxidized to the corresponding 6-nitroso derivative (6-NOBP) as the main metabolite (2). Since ADPRT is located in the nuclear matrix (3,4) and most of the cytochrome P450 resides in the endoplasmic reticulum which is contiguous with the nuclear membrane (5), generation of 6-NOBP near ADPRT is likely. This suggested that the exact cellular significance of this oxidation path be investigated with respect to ADPRT.