title: Expression and regulation of glycogen phosphorylase in preneoplastic and neoplastic hepatic lesions in rats.
abstract: Glycogen phosphorylase (PHO) was demonstrated immunocytochemically and enzyme histochemically in cryostat sections of liver from rats treated for 7 weeks with N-nitrosomorpholine (120 mg/l and 200 mg/l drinking water) and from untreated controls. The activity and distribution of PHO protein were studied in normal liver and correlated with morphologically defined stages of hepatic tumour development. In normal liver the amount of enzyme protein, as visualized by the immunoperoxidase method using antibodies against phosphorylase, showed some heterogeneity within the liver lobule. The intralobular and intracellular distribution of PHO protein was the same as that of glycogen, namely coarse and granular in periportal hepatocytes and very fine in perivenular cells. In glycogen storage foci the amount of PHO protein was increased. In contrast, PHO activity was generally decreased. In other preneoplastic and neoplastic lesions such as mixed cell foci, neoplastic nodules and hepatocellular carcinomas, PHO protein was increased in all glycogen-loaded cells while PHO activity was reduced. In all glycogen-poor and basophilic cells, both PHO protein and PHO activity were decreased or absent. It was concluded that the decrease in PHO activity in glycogen storage foci was not the direct consequence of genetic changes leading to a loss in enzyme protein but was due to a defect in the cascade of phosphorylation processes resulting in active PHO. Alteration in gene expression leading to a loss of PHO protein was a late event in the process of hepatocarcinogenesis.
mesh_terms: D000818:Animals; D004789:Enzyme Activation; D007124:Immunoenzyme Techniques; D008099:Liver / Q000201:enzymology; D008114:Liver Neoplasms, Experimental / Q000201:enzymology*; D008297:Male; D006005:Phosphorylases / Q000378:metabolism*; D011230:Precancerous Conditions / Q000201:enzymology*; D051381:Rats
chemical_list: D006005:Phosphorylases