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- W2056511972 abstract "Adenylate cyclase (AC) activity was demonstrated histochemically using adenylate-(beta,gamma-methylene)diphosphate as substrate in cryostat sections of livers from 45 rats treated for 7-10 weeks with N-nitrosomorpholine (NNM) (120 mg/l drinking water) and from nine untreated control rats. The enzyme patterns of normal tissue, preneoplastic and neoplastic lesions were characterized and correlated with the morphologically defined stages of tumour development in the liver. Light microscopically, the enzyme activity of normal tissue was restricted to the plasma membrane, and was most pronounced along the bile canaliculi of the hepatocytes. In glycogen storage foci and mixed cell foci induced by NNM no, or only very weak, AC activity was visible. In the cells of neoplastic nodules and hepatocellular carcinomas AC activity was also clearly reduced. However, in small parts of the plasma membrane which lined lumina resembling normal bile canaliculi and in cytoplasmic vesicles closely associated with these structures, some AC activity was occasionally detected by light and electron microscopy. Whereas the tissue of normal appearance surrounding the lesions showed a marked increase in AC activity in the presence of glucagon, forskolin and cholera toxin. AC activity in the preneoplastic and neoplastic liver lesions could not, or could only weakly, be stimulated by this treatment. As demonstrated in serial sections of the foci, the reduction in AC activity corresponded to changes in the activity of other enzymes studied earlier in the same model. Thus the reduction in AC activity was accompanied by a decrease in the activity of glucose-6-phosphatase and glycogen phosphorylase, and by an increase in the activity of glucose-6-phosphate dehydrogenase. The results support the concept that the focal changes in the activity of many enzymes (including those of carbohydrate metabolism) during hepatocarcinogenesis are the consequence of aberrations in superordinate regulatory mechanisms of cell metabolism." @default.
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- W2056511972 date "1986-01-01" @default.
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- W2056511972 title "Loss of adenylate cyclase activity in preneoplastic and neoplastic lesions induced in rat liver by <i>N</i>-nitrosomorpholine" @default.
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- W2056511972 doi "https://doi.org/10.1093/carcin/7.4.567" @default.
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