The mechanisms of UV radiation in the development of malignant melanoma

Abstract

The sunlight was one of the first agents recognized to be carcinogenic for humans. There is convincing evidence from epidemiologic studies that exposure to solar radiation is the major cause of cutaneous melanoma in light-pigmented populations and plays a role in the increasing incidence of this malignancy. The molecular mechanisms by which UV radiation exerts its varied effects are not completely understood, however, it is considered that UVA and UVB are equally critical players in melanoma formation. Whereas UVA can indirectly damage DNA through the formation of reactive oxygen radicals, UVB can directly damage DNA causing the apoptosis of keratinocytes by forming the sunburn cells. Besides action through mutations in critical regulatory genes, UV radiation may promote cancer through indirect mechanisms, e.g. immunosuppression and dysregulation of growth factors. The carcinogenic process probably involves multiple sequential steps, some, but not all of which involve alterations in DNA structure.