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Decrease of epidermal histidase activity by tumor-promoting phorbol esters.

N H Colburn, S Lau, R Head

    Cancer Research
    |November 1, 1975
    PubMed
    Summary
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    The skin tumor promoter 12-O-tetradecanoyl phorbol-13-acetate (TPA) significantly decreases epidermal histidase activity in mice. This effect is linked to tumor promotion, not initiation, and is observed with other promoters like Tween 60.

    Area of Science:

    • Dermatology
    • Biochemistry
    • Carcinogenesis

    Background:

    • 12-O-tetradecanoyl phorbol-13-acetate (TPA) is a potent skin tumor promoter.
    • Specific functional changes induced by TPA in epidermal cells are not well understood.
    • Epidermal histidase (L-histidine ammonia lyase) is present in normal epidermis but absent in squamous cell carcinomas.

    Purpose of the Study:

    • To investigate the effects of TPA on epidermal histidase activity.
    • To determine if changes in histidase activity correlate with skin tumor promotion.

    Main Methods:

    • Hairless mice were treated topically with TPA.
    • Epidermal histidase activity was measured in postmitochondrial supernatants.
    • Enzyme activity was compared between TPA-treated and control groups.

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    Main Results:

    • TPA treatment caused a dose-dependent decrease in epidermal histidase specific activity.
    • The decrease in histidase activity occurred within 12 hours and recovered by 5 days post-treatment.
    • Other phorbol derivatives and the unrelated promoter Tween 60 also decreased histidase, while initiators did not.

    Conclusions:

    • TPA-induced decrease in epidermal histidase is associated with tumor promotion, not initiation.
    • This finding provides insight into the specific functional aberrations caused by TPA during skin carcinogenesis.