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Transnitrosation by nitrosamines in vivo

W Lijinsky, M D Reuber

    IARC Scientific Publications
    |January 1, 1982
    PubMed
    Summary

    In vivo transnitrosation significantly enhanced carcinogenicity of certain nitrosamines, particularly in the liver, when combined with morpholine and a catalyst. This highlights the critical role of transnitrosation in chemical carcinogenesis.

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    Area of Science:

    • Toxicology
    • Carcinogenesis
    • Organic Chemistry

    Background:

    • Nitrosamines are a class of chemicals known for their carcinogenic potential.
    • In vivo transnitrosation is a process where a nitrosyl group is transferred between molecules within a living organism.
    • The role of transnitrosation in the formation and carcinogenicity of nitrosamines requires further elucidation.

    Purpose of the Study:

    • To investigate the significance of in vivo transnitrosation in the carcinogenesis induced by nitrosamines.
    • To evaluate the effect of combining morpholine with various nitrosamines, with and without a transnitrosation catalyst (sodium thiocyanate).
    • To determine the specific tumor types and frequencies associated with different nitrosamine exposures and transnitrosation conditions.

    Main Methods:

    • Feeding studies involving mixtures of morpholine and four different nitrosamines to rats over most of their lifespan.
    • Inclusion of sodium thiocyanate as a transnitrosation catalyst in specific experimental groups.
    • Monitoring of tumor incidence, types, and survival rates across all treatment groups.

    Main Results:

    • None of the four tested nitrosamines induced significant liver tumors when administered alone.
    • Nitrosophenylbenzylamine and nitroso-N-methylpiperazine induced tumors in the spleen, upper gastrointestinal tract, and nasal cavity, respectively.
    • Combinations of nitrosoproline or nitrosohydroxyproline with morpholine, especially in the presence of sodium thiocyanate, significantly increased the frequency of hepatic (liver) tumors. Similar effects were observed with nitrosophenylbenzylamine and nitrosomethylpiperazine when combined with morpholine and thiocyanate.

    Conclusions:

    • In vivo transnitrosation, facilitated by morpholine and sodium thiocyanate, plays a critical role in enhancing the liver carcinogenicity of certain nitrosamines.
    • The presence of a transnitrosation catalyst significantly increases tumor yield in specific organs, underscoring the importance of this metabolic pathway in chemical carcinogenesis.
    • Dietary factors and co-ingested substances can profoundly influence the carcinogenic potential of nitrosamines.

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