title: Changes in gamma-glutamyltransferase activity during N-2-fluorenylacetamide-induced rat hepatocarcinogenesis.
abstract: Changes in gamma-glutamyltransferase (GGT) activity throughout the course of rat hepatocarcinogenesis induced by brief dietary exposure to N-2-fluorenylacetamide (2-FAA) followed by promotion with dietary phenobarbital (PB) were studied. By examination of changes in total GGT activity and its histochemical localization, the effects of initiator and promoter on this enzyme can be clearly differentiated. Both 2-FAA and PB increase total GGT activity in grossly normal liver, PB causing a tenfold greater increase than that caused by 2-FAA. Although the elevation of GGT activity in livers of rats sequentially treated with 2-FAA-PB was not additive or synergistic, the course of increase was distinct from that of either 2-FAA- or PB-caused changes in activity, suggesting that 2-FAA and PB interact to alter the GGT phenotype of sequentially treated animals. GGT activity in neoplasms induced by either 2-FAA or 2-FAA-PB was highly variable, i.e., from nearly basal levels to those 170-fold greater than basal. Lesions induced by 2-FAA without PB promotion had elevated GGT, indicating that PB is not required to produce GGT-positive neoplasms by this protocol. Histochemically, changes in GGT activity occurred in both hepatocytes and nonhepatocyte cell populations in a characteristic, treatment-dependent manner, well-correlated with total GGT activity. Treatment with 2-FAA, especially that with 2-FAA-PB, induced primarily focal and nodular GGT activity patterns. PB alone produced no GGT-positive foci, but it did cause GGT-positive ductular proliferation. Continued PB exposure produced a GGT activity pattern which clearly defined the interlobular regions of the liver; no similar staining pattern was seen in either 2-FAA-treated or 2-FAA-PB-treated livers. These results indicate that an initiator and one of its promoters, combined and individually, alter GGT activity in a characteristic manner over the course of hepatocarcinogenesis. Moreover, the effects of the promoter on GGT activity are dependent on whether or not prior exposure to initiator has occurred.
mesh_terms: D015073:2-Acetylaminofluorene; D000818:Animals; D003043:Cocarcinogenesis; D004032:Diet; D006651:Histocytochemistry; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced / Q000201:enzymology*; D010634:Phenobarbital / Q000494:pharmacology; D051381:Rats; D013268:Stimulation, Chemical; D005723:gamma-Glutamyltransferase / Q000378:metabolism*
chemical_list: D015073:2-Acetylaminofluorene; D005723:gamma-Glutamyltransferase; D010634:Phenobarbital