Decrease in glucokinase and glucose-6-phosphatase and increase in hexokinase in putative preneoplastic lesions of rat liver.
Preneoplastic liver lesions were produced in female Wistar rats by oral administration of 2-acetylaminofluorene for 165 days succeeded by a carcinogen-free standard diet up to 420 days. During the treatment numerous altered hepatic foci (AHF) and hyperplastic nodules (HN) were detected histochemically by a focal decrease or lack of adenosine-5-triphosphatase and glucose-6-phosphatase (G-6-Pase) activities. In addition, the immunohistochemically demonstrable amount of L-type pyruvate kinase was clearly reduced. The histochemically demonstrated decrease of G-6-Pase was substantiated by microbiochemical determination of the enzyme activity in microdissected material. Moreover, during the experimental period a continuous decrease in glucokinase and an increase in hexokinase was detected microbiochemically within AHF and HN. These alterations indicate a shift in the carbohydrate metabolism from gluconeogenesis to glucose utilization and pentose-phosphate-pathway for biosynthesis of nucleic acids. Beside other oncofetal markers, HK may be used as indicator of the early stages of liver carcinogenesis.
D015073:2-Acetylaminofluorene; D000251:Adenosine Triphosphatases / Q000378:metabolism; D000818:Animals; D005260:Female; D005941:Glucokinase / Q000378:metabolism*; D005952:Glucose-6-Phosphatase / Q000378:metabolism*; D006593:Hexokinase / Q000378:metabolism*; D006651:Histocytochemistry; D008113:Liver Neoplasms / Q000139:chemically induced / Q000201:enzymology*; D011230:Precancerous Conditions / Q000139:chemically induced / Q000201:enzymology*; D051381:Rats; D011919:Rats, Inbred Strains
D015073:2-Acetylaminofluorene; D006593:Hexokinase; D005941:Glucokinase; D005952:Glucose-6-Phosphatase; D000251:Adenosine Triphosphatases