Inflammatory Doses of UV May Not Be Necessary for Skin Carcinogenesis

Authors

  • Gary M. Halliday,

    Corresponding author
    1. Dermatology Research Laboratories, Melanoma and Skin Cancer Research Institute  and Bosch Institute at the University of Sydney, Sydney, NSW, Australia
      *Corresponding author email: garyh@med.usyd.edu.au (Gary Halliday)
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  • J. Guy Lyons

    1. Dermatology Research Laboratories, Melanoma and Skin Cancer Research Institute  and Bosch Institute at the University of Sydney, Sydney, NSW, Australia
    2. Sydney Head and Neck Cancer Research Institute, Sydney Cancer Centre,  Royal Prince Alfred Hospital, Sydney, NSW, Australia
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  • This paper is part of a special issue dedicated to Professor Hasan Mukhtar on the occasion of his 60th birthday.

*Corresponding author email: garyh@med.usyd.edu.au (Gary Halliday)

Abstract

The UV wavelengths in sunlight are the main cause of skin cancer in humans. Sunlight causes gene mutations, immunosuppression and, at higher doses, inflammation. While it is clear that immunosuppression and gene mutations are essential biologic events via which UV causes skin cancer, the requirement for UV-induced inflammation is less certain. Both the UVB (290–320 nm) and UVA (320–400 nm) wavebands within sunlight can cause skin cancer, gene mutations and immunosuppression. However, UVB, but not UVA, at realistic doses can cause inflammation, and UVB induces skin cancer, immunosuppression and gene mutations at doses much lower than those required to cause inflammation. Inflammation enhances skin carcinogenesis, but may not be UV induced, and inflammatory mediators at doses too low to cause inflammation may be required. UV-induced mutations can cause epidermal cells to make proinflammatory factors or to induce them in the surrounding stroma, creating an oxidizing environment in which additional oncogenic mutations are likely to take place, even in the absence of UV. Our hypothesis is therefore that subinflammatory doses of both UVA and UVB cause benign skin tumors. One of the effects of sunlight-induced mutations may be the production of inflammatory mediators that enhance carcinogenesis.

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