The dark side of the light: mechanisms of photocarcinogenesis

• Published in: Clinics in dermatology Vol. 34; no. 5; pp. 563 - 570
• Main Authors: Coelho, Margarida Moura Valejo, MD, MSc, Matos, Tiago R., MD, MSc, Apetato, Margarida, MD
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.09.2016
• Subjects: Antigen Presentation - radiation effects; Carcinogenesis - radiation effects; Cytokines - radiation effects; Dermatology; DNA Damage - radiation effects; Humans; Immune Tolerance - radiation effects; Mutagenesis - radiation effects; Neoplasms, Radiation-Induced; Oxidative Stress - radiation effects; Skin - radiation effects; Skin Diseases - radiotherapy; Skin Neoplasms - etiology; T-Lymphocytes, Regulatory - radiation effects; Ultraviolet Therapy - adverse effects; cyclobutane pyrimidine dimers; OGG1; cluster of differentiation; ICAM-1; platelet-activating factor; serotonin; IFN-γ; RNS; 6–4 photoproducts; prostaglandin E 2; Dewar valence isomers; T h; intercellular adhesion molecule-1; DEWs; BCC; IL; base excision repair; UV(R); non-melanoma skin cancer; urocanic acid; regulatory T cells; transforming growth factor-β; guanine; NKT; ROS; Langerhans cells; basal cell carcinoma; CTLA; NAD(P)H; 5-HT; CGRP; helper T cells; A; interferon-γ; photoimmunosuppression; C; CPDs; antigen-presenting cell; COX-2; G; 7,8-dihydro-8-oxoguanosine; PGE 2; α-melanocyte stimulating hormone; ultraviolet (radiation); PTCH; Patched; photoproducts; cytosine; deoxyribonucleic acid; T; reactive oxygen species; miRNA; reactive nitrogen species; TGF-β; α-MSH; FoxP3; interleukin; forkhead box P3; LCs; CD; photosensitized reactions; signature mutations; T reg; calcitonin gene-related peptide; 8-oxoguanine DNA glycosylase-1; 8-oxoG; NMSC; cytotoxic T-lymphocyte-associated protein; BER; natural killer T cells; SCC; UCA; APC; nicotinamide adenine dinucleotide (phosphate); PAF; TNF-α; photocarcinogenesis; 6–4 PPs; DNA; tumor necrosis factor-α; adenine; microRNA; cyclooxygenase 2; NER; nucleotide excision repair; squamous cell carcinoma; thymine
• ISSN: 0738-081X; 1879-1131
• DOI: 10.1016/j.clindermatol.2016.05.022

Abstract Ultraviolet radiation (UVR) can have a beneficial biological 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 the biologic impact of UVR and its role in skin cancer development.