Journal article

Publication year: 1986

Pages: 1351-1357

Journal: Carcinogenesis: Integrative Cancer Research

Volume number: 7

Issue number: 8

ISSN: 0143-3334

eISSN: 1460-2180

DOI Link: https://doi.org/10.1093/carcin/7.8.1351

Publisher: Oxford University Press

Abstract: 
Pyruvate kinase (PK) isoenzymes, rate limiting for the last steps of glycolysis, were studied in normal rat liver, putative preneoplastic foci, neoplastic nodules and hepatocellular carcinoma. These lesions were produced by an initiation-promotion protocol: treatment with a single dose of N-nitrosomorpholine (NNM) was followed by feeding diets containing phenobarbital (PB) or .alpha.-hexachloroclohexane (.alpha.-HCH), or basal diet. PK was demonstrated by immunocytochemistry on histological sections with antibodies specifically directed against the L and M2 isoenzymes, by electrophoretic separation of isoenzymes in homogenates from liver and larger tumors, and by electrophoretic separation of isoenzymes in parenchymal and stromal cells isolated from liver and tumors. Immunocytochemistry showed decreased of L-PK (L-PK-) in hepatocytes of most of the foci, nodules and carcinomas. Most L-PK- foci showed increased in .gamma.-glutamyltransferase (.gamma.-GT) and epoxide hydrolase (EH). PB or .alpha.-HCH treatment further decreased expression of L-PK in foci, but not in normal liver. Cells and foci with enhanced L-PK (L-PK+) were also found after carcinogen treatment. These did not show increases of .gamma.-GT or EH or any distinct morphological alterations with the exception of some which were basophilic (''tigroid'') in H and E stained sections. No L-PK+ tumors were found. We could not demonstrate the M2-type PK in parenchymal cells of liver or any of the lesions described above. This isoenzyme was restricted to stromal cells in normal rat liver and in all stages of carcinogenesis as shown by immunohistology and by electrophoresis of preparations from isolated cell populations. However, stromal cells from hepatocellular carcinomas exhibited a 3-fold increase of M2-PK compared with stromal cells from normal liver. These results do not support an isoenzyme shift from L to M2-PK in the course of malignant transformation of hepatocytes as suggested previously.

Harvard Citation style: REINACHER, M., EIGENBRODT, E., GERBRACHT, U., ZENK, G., TIMMERMANNTROSIENER, I., BENTLEY, P., et al. (1986) PYRUVATE-KINASE ISOENZYMES IN ALTERED FOCI AND CARCINOMA OF RAT-LIVER, Carcinogenesis: Integrative Cancer Research, 7(8), pp. 1351-1357. https://doi.org/10.1093/carcin/7.8.1351

APA Citation style: REINACHER, M., EIGENBRODT, E., GERBRACHT, U., ZENK, G., TIMMERMANNTROSIENER, I., BENTLEY, P., WAECHTER, F., & SCHULTEHERMANN, R. (1986). PYRUVATE-KINASE ISOENZYMES IN ALTERED FOCI AND CARCINOMA OF RAT-LIVER. Carcinogenesis: Integrative Cancer Research. 7(8), 1351-1357. https://doi.org/10.1093/carcin/7.8.1351