Autoradiographic studies on in vivo covalent binding of N-hydroxy-2-acetylaminofluorene in rat liver containing gamma-glutamyltranspeptidase-positive foci. The effect of the sulfation-inhibitor pentachlorophenol.

The role of sulfation in the covalent binding of [ring-3H]-N-hydroxy-2-acetylaminofluorene (N-OH-AAF) in rat liver containing gamma-glutamyltranspeptidase-positive (GGT+) foci was studied in vivo by autoradiography. GGT+ foci were induced by initiation with diethylnitrosamine, followed by a selection protocol consisting of a 2-week exposure to 2-aminofluorene in the drinking water and a single administration of CCl4. Both surrounding ('normal') liver tissue and, to a lesser extent, GGT+ foci covalently bound N-OH-AAF, administered 10 days after selection. The sulfation inhibitor, pentachlorophenol (PCP), reduced the covalent binding of N-OH-AAF in cells surrounding the foci. However, PCP had no effect on binding of radiolabel in GGT+ foci. Thus, reduced sulfotransferase activity may contribute to the resistance of GGT+ preneoplastic lesions to carcinogen cytotoxicity. The results suggest also, that cells in GGT+ foci are able to bind N-OH-AAF covalently by a sulfotransferase-independent pathway.