Formation of UV-induced DNA damage contributing to skin cancer development

Abstract

UV-induced DNA damage plays a key role in the initiation phase of skin cancer. When left unrepaired or when damaged cells are not eliminated by apoptosis, DNA lesions express their mutagneic properties, leading to the activation of proto-oncogene or the inactivation of tumor suppression genes. The chemical nature and the amount of DNA damage strongly depend on the wavelength of the incident photons. The most energetic part of the solar spectrum at the Earth's surface (UVB, 280-320 nm) leads to the formation of cyclobutane pyrimidine dimers (CPDs) and pyrimidine (6-4) pyrimidone photoproducts (64PPs). Less energetic but 20-times more intense UVA (320-400 nm) also induces the formation of CPDs together with a wide variety of oxidatively generated lesions such as single strand breaks and oxidized bases. Among those, 8-oxo-7,8-dihydroguanine (8-oxoGua) is the most frequent since it can be produced by several mechanisms. Data available on the respective yield of DNA photoproducts in cells and skin show that exposure to sunlight mostly induces pyrimidine dimers, which explains the mutational signature found in skin tumors, with lower amounts of 8-oxoGua and strand breaks. The present review aims at describing the basic photochemistry of DNA and discussing the quantitative formation of the different UV-induced DNA lesions reported in the literature. Additional information on mutagenesis, repair and photoprotection is briefly provided.

The real protection of facial sunscreens

“…D ear E ditor , The harmful effects of solar radiation exposure on human skin are well known . Both ultraviolet (UV)B and UVA radiation induce DNA damage, leading the formation of molecules, such as pyrimidine dimers and 6–4 photoproducts, which play a key role in the development of skin cancer . Despite the increasing awareness of the harmful effects of the sun and use of sun protection, 70–90% of basal cell carcinomas develop in the sun‐exposed head and neck region, and 5–10% of all skin cancers occur on the eyelids …”

Triplet‐Induced Lesion Formation at CpT and TpC Sites in DNA

“…The damaging effects can be ascribed to the ultraviolet part of the solar spectrum inducing the direct or indirect formation of different types of DNA lesions. The most abundant lesions occur between neighboring pyrimidine bases (thymine and cytosine) and include the formation of cyclobutane pyrimidine dimers (CPDs) and pyrimidine (6‐4) pyrimidone photoproducts . These lesions are known to lead to mutations in the genome and are regarded as precursors of skin cancer .…”

Photoprotection of the future: challenges and opportunities

“…This might, at least partially, be explained by the fact that nutritional supplements such as carotenoids can act as antioxidants. Accordingly, UVB‐induced erythema mainly results from the direct generation of DNA damage, that is cyclobutane pyrimidine dimers (CPDs), by UVB, whereas UVA effects are mediated to a large extend by oxidative stress …”