The role of N-sulfation in the N-hydroxy-2-acetylaminofluorene-mediated outgrowth of diethylnitrosamine-initiated hepatocytes to gamma-glutamyltranspeptidase-positive foci in male rat liver.
The ability of N-hydroxy-2-acetylaminofluorene (N-OH-AAF) to promote the appearance of gamma-glutamyltranspeptidase-positive (GGT+) foci initiated by diethylnitrosamine (DEN) was studied in a slightly modified Solt and Farber protocol. This protocol consisted of the following treatments: initiation with a single dose of DEN followed by selection/promotion with several non-necrogenic doses of N-OH-AAF and partial hepatectomy. Treatment with N-OH-AAF resulted in a 25-fold increase of the liver volume occupied by GGT+ cells as compared to controls. The role of N-sulfation of N-OH-AAF in the GGT+ foci-selecting activity of N-OH-AAF was studied using the sulfotransferase inhibitor pentachlorophenol (PCP). Inhibition of the N-sulfation pathway with PCP during selection with N-OH-AAF resulted in a greater than 80% decrease in the volume occupied by GGT+ cells, without effects on the number of GGT+ foci generated with this protocol. Also, PCP reduced the number of so called oval and bile duct cells generated by the N-OH-AAF/partial hepatectomy treatment. It is concluded that N-sulfation of N-OH-AAF is responsible for the N-OH-AAF-mediated outgrowth of DEN-initiated hepatocytes to preneoplastic GGT+ foci.
D015073:2-Acetylaminofluorene / Q000031:analogs & derivatives*; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D003043:Cocarcinogenesis; D004052:Diethylnitrosamine / Q000494:pharmacology; D006881:Hydroxyacetylaminofluorene / Q000378:metabolism / Q000494:pharmacology*; D008099:Liver / Q000166:cytology / Q000201:enzymology*; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced*; D008297:Male; D010416:Pentachlorophenol / Q000494:pharmacology; D011230:Precancerous Conditions / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology*; D051381:Rats; D011919:Rats, Inbred Strains; D013431:Sulfates / Q000378:metabolism*; D015238:Sulfotransferases / Q000037:antagonists & inhibitors*; D005723:gamma-Glutamyltransferase / Q000378:metabolism*
D013431:Sulfates; D004052:Diethylnitrosamine; D006881:Hydroxyacetylaminofluorene; D015073:2-Acetylaminofluorene; D010416:Pentachlorophenol; D005723:gamma-Glutamyltransferase; D015238:Sulfotransferases