The dark side of the light: mechanisms of photocarcinogenesis

Abstract

Ultraviolet radiation (UVR) can have a beneficial biologic impact on skin, but it is also the most significant environmental risk factor for skin cancer development. Photocarcinogenesis comprises a complex interplay between the carcinogenic UVR, skin, and the immune system. UVB is absorbed by the superficial skin layers and is mainly responsible for direct DNA damage, which, if unrepaired, can lead to mutations in key cancer genes. UVA is less carcinogenic, penetrates deeper in the dermis, and mainly causes indirect oxidative damage to cellular DNA, proteins, and lipids, via photosensitized reactions. UVR not only induces mutagenesis, altering proliferation and differentiation of skin cells, but also has several immunosuppressive effects that compromise tumor immunosurveillance by impairing antigen presentation, inducing suppressive cells, and modulating the cytokine environment. This review focuses upon molecular and cellular effects of UVR, regarding its role in skin cancer development.

Significance of Wild-Type p53 Signaling in Suppressing Apoptosis in Response to Chemical Genotoxic Agents: Impact on Chemotherapy Outcome

“…The plethora of DNA lesions include DNA strand breaks and base alterations induced by ionizing radiation and chemical agents that generate reactive oxygen species, DNA alkylation and formation of abasic sites induced by alkylating agents, bulky DNA lesions induced by ultraviolet light (UV), DNA interstrand crosslinks induced by bifunctional alkylating agents and platinum drugs, and DNA-protein crosslinks arising from a wide range of chemicals, such as chemotherapeutic drugs and formaldehyde [1,2,3,4]. Constitutively available DNA repair processes deal with low levels of genomic injury and assist in ameliorating the detrimental effects of such agents.…”

MITF and UV responses in skin: From pigmentation to addiction

“…Even though the sun emits a significant amount of UVR, only 5% of the radiation actually reaches the earth's surface, of which approximately 95% is UVA and 1%–10% is UVB. Almost 100% of UVC is filtered out by the atmosphere and the ozone layer (Valejo Coelho, Matos, & Apetato, ). Therefore, research has paid most attention to the biological consequences of UVA and UVB exposure to the skin.…”

“…UV‐induced DNA damage signatures have been found in approximately 46% of known driver mutations in human BRAF V600E melanomas, including CDKN2A, TP53, NF1, RAC1, and PTEN (Hodis et al., ; Michaloglou et al., ; Xia et al., ). Separate from its mutagenic activity, UV acts as an immunosuppressant by disturbing skin antigen presentation and recruiting suppressive immunological cells through cytokines and other mediators, contributing to tumor growth and survival (reviewed in Valejo Coelho et al., ). Of late, the White group demonstrated UVB as a critical extrinsic factor to promote the initiation of melanoma through melanocyte stem cells in an inflammation‐dependent manner (Moon et al., ).…”

“…Almost 100% of UVC is filtered out by the atmosphere and the ozone layer (Valejo Coelho, Matos, & Apetato, 2016). Therefore, research has paid most attention to the biological consequences of UVA and UVB exposure to the skin.…”

Current Approach to Phototherapy Applications in Dermatology Practice: Part 1. History, Lamps, Ultraviolet Radiation Levels Measurement and Phototherapy Modalities

“…Deri kanserlerinin gelişiminde iki anahtar faktör olan, hücre proliferasyonu ve farklılaşmasında değişim ve immünsüpresyona yol açan mutajenik olayları tetikler. Bu nedenle, fototerapinin karsinojenik potansiyeli konusundaki endişeler yerindedir (30). Ancak dar bant UVB'nin deri kanseri insidansında artışa yol açıp açmadığı konusunun netleşebilmesi için, seans sayısı fazla olan hastaları içeren, daha uzun izlem süreli çalışmalara gereksinim vardır.…”