Decrease in glucokinase and glucose-6-phosphatase and increase in hexokinase in putative preneoplastic lesions of rat...

Area of Science:

• Hepatology
• Carcinogenesis
• Biochemistry

Background:

• Preneoplastic liver lesions are critical precursors to hepatocellular carcinoma.
• Understanding metabolic alterations in early carcinogenesis is vital for timely diagnosis and intervention.

Purpose of the Study:

• To investigate the metabolic changes associated with preneoplastic liver lesions induced by 2-acetylaminofluorene in Wistar rats.
• To identify potential biomarkers for early detection of liver carcinogenesis.

Main Methods:

• Induction of preneoplastic liver lesions using 2-acetylaminofluorene in Wistar rats.
• Histochemical analysis for adenosine-5-triphosphatase and glucose-6-phosphatase (G-6-Pase) activities.
• Immunohistochemical detection of L-type pyruvate kinase.
• Microbiochemical determination of enzyme activities (G-6-Pase, glucokinase, hexokinase) in microdissected lesions.

Main Results:

• Altered hepatic foci (AHF) and hyperplastic nodules (HN) showed decreased adenosine-5-triphosphatase and G-6-Pase activities.
• A reduction in L-type pyruvate kinase was observed in preneoplastic lesions.
• Microbiochemical analysis confirmed decreased G-6-Pase, decreased glucokinase, and increased hexokinase (HK) within AHF and HN.
• These findings indicate a metabolic shift from gluconeogenesis to glucose utilization and the pentose-phosphate pathway.

Conclusions:

• The observed metabolic alterations in preneoplastic liver lesions suggest a shift towards increased glucose utilization and nucleic acid biosynthesis.
• Hexokinase (HK) activity may serve as a valuable indicator for the early stages of liver carcinogenesis, alongside other oncofetal markers.