Clinical observations and epidemiologic studies indicate that the sun is the primary stimus for most human skin can formation. However, investigations directly confirming this association as well as defining the action spectra, time-dose relationships, energy level requirements, etc., have been confined to animal experimentation. Studies in which gross methods are used indicate that the experimental carcinogenic action spectrum falls primarily between 280 and 320 nm. Quantitative studies and
tumor promotion investigations indicate that UV-induced
cancer formation begins with the initial exposure. Heat, wind, and moisture stimulate UV
carcinogenesis. Also, exogenous chemicals may influence
carcinogenesis as
photosensitizers such as
8-MOP, as additive
carcinogens as noted with DMBA, or as promoters as described for
Croton oil,
retinoic acid, and
BCNU. Qualitative studies indicate that progressive alterations occur in the epidermal-dermal basement membrane and dermal conncecive tissue and
mucopolysaccharides associated with the progressive development of epidermal
cancers.
Malignant melanomas have also been induced experimentally in hairless mice with UV energy. Mechanistically, immunologic alterations and effects on
DNA have received the most attention.
Tumor-specific antigenicity as well as
antigen deletion has been demonstrated. Immune suppression by
antilymphocyte serum and certain chemicals has led to stimulation of
tumor development. Perhaps the most exciting new information relates to the demonstration that chronically UV-irradiated mice have not rejected highly antigenic UV-induced
cancers. This indicated that UV irradiation specifically altered the immunologic responses of the animals to these
tumors. Within recent years, the influence of DNA injury and repair on cutaneous
carcinogenesis has received a great deal of attention. This has been partly due to the demonstration of defective repair of UV-induced DNA damage in patients with XP. The primary photosensitive problem in these patients is an inordinate sensitivity to the carcinogenic effects of sunlight. However, correlation of DNA injury and repair directly with
cancer formation has not been accomplished.