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Decrease in L-type pyruvate kinase activity in rat liver by some promoters of hepatocarcinogenesis.

S Yanagi, M Sakamoto, Y Ninomiya

    Journal of the National Cancer Institute
    |October 1, 1984
    PubMed
    Summary

    Hepatocarcinogens and promoters like phenobarbital significantly decrease liver L-type pyruvate kinase (L-PK) activity in rats. This L-PK decrease may serve as a biomarker for identifying hepatic promoters.

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    Area of Science:

    • Biochemistry
    • Hepatology
    • Toxicology

    Background:

    • Liver pyruvate kinase (PK) exists in L-type (L-PK) and K-type (K-PK) isoforms.
    • Certain chemical agents can initiate or promote hepatocarcinogenesis, impacting liver enzyme activity.
    • Understanding enzyme modulation by carcinogens and promoters is crucial for cancer research.

    Purpose of the Study:

    • To investigate the effect of hepatocarcinogens and promoters on L-type pyruvate kinase (L-PK) activity in Wistar rat liver.
    • To explore the potential of L-PK activity as a screening tool for hepatic promoters.
    • To compare the effects of promoting and non-promoting agents on L-PK activity.

    Main Methods:

    • Wistar rats were continuously fed specific agents, including 3'-methyl-4-dimethylaminoazobenzene (3'-MeDAB), phenobarbital (PB), and dichlorodiphenyltrichloroethane.

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  • L-type pyruvate kinase (L-PK) and K-type pyruvate kinase (K-PK) activities were measured.
  • Control groups received non-promoting agents like amobarbital and diphenylhydantoin.

    • Main Results:

    • Continuous feeding of hepatocarcinogen 3'-MeDAB and hepatic promoters PB and dichlorodiphenyltrichloroethane significantly decreased L-PK activity over 4 weeks.
    • Non-promoting agents amobarbital and diphenylhydantoin caused only temporary decreases in L-PK activity.
    • PB-induced L-PK depression was reversible, dose-dependent, and organ-specific.
    • K-PK activity was induced by carcinogens (diethylnitrosamine, CCl4, 3'-MeDAB) but not by non-promoting initiators or PB.

    Conclusions:

    • A promoter-specific decrease in hepatic L-PK activity was observed in Wistar rats.
    • The observed decrease in L-PK activity shows potential as a screening method for hepatic promoters.
    • Further extensive research is required to establish a general conclusion due to limited data.