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Tumor initiation by N-acyloxy derivatives of piperidine and N-arylacetamides

J D Scribner, T J Slaga

    Journal of the National Cancer Institute
    |February 1, 1975
    PubMed

    Insights

    Four N-acetoxy-N-arylacetamides, previously identified as local sarcomagens in rats, also initiate tumor formation in mouse skin. This study establishes their carcinogenic potential across different species and tissues.

    Area of Science:

    • Chemical carcinogenesis
    • Toxicology
    • Dermatology

    Background:

    • N-Acetoxy-N-arylacetamides are known local sarcomagens in rats.
    • Understanding their carcinogenic mechanisms is crucial for risk assessment.

    Purpose of the Study:

    • To evaluate the tumor-initiating activity of N-acetoxy-N-arylacetamides in mouse skin.
    • To investigate the carcinogenic potential of related compounds, N-benzoyloxypiperidines.

    Main Methods:

    • Topical application of N-acetoxy-N-arylacetamides and N-benzoyloxypiperidines to mouse skin.
    • Assessment of tumor initiation and development.

    Main Results:

    • Four N-acetoxy-N-arylacetamides demonstrated significant tumor-initiating activity in mouse skin.
    • A clear order of carcinogenic potency was observed: N-acetoxy-2-acetamidophenanthrene > N-acetoxy-4-acetamino-stilbene ≈ N-acetoxy-2-acetamido-fluorene > N-acetoxy-4-acetamidobiphenyl.
    • Two substituted N-benzoyloxypiperidines also exhibited initiating activity.

    Conclusions:

    • N-acetoxy-N-arylacetamides possess carcinogenic potential as tumor initiators in mouse skin, extending their known activity from rats.
    • These findings highlight the broader implications of these compounds in chemical carcinogenesis and warrant further investigation into their mechanisms of action.

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