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Oxidative Stress and Genotoxicity in Melanoma Induction: Impact on Repair Rather Than Formation of DNA Damage?
Author(s) -
Douki Thierry
Publication year - 2020
Publication title -
photochemistry and photobiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.818
H-Index - 131
eISSN - 1751-1097
pISSN - 0031-8655
DOI - 10.1111/php.13278
Subject(s) - pyrimidine dimer , dna damage , melanoma , oxidative stress , mutagenesis , cancer research , genotoxicity , dna , reactive oxygen species , cell , biology , skin cancer , dna repair , epidermis (zoology) , mutation , gene , chemistry , cancer , microbiology and biotechnology , genetics , biochemistry , toxicity , organic chemistry , anatomy
Keratinocytes and melanocytes, two cutaneous cell types located within the epidermis, are the origin of most skin cancers, namely carcinomas and melanomas. These two types of tumors differ in many ways. First, carcinomas are almost 10 times more frequent than melanomas. In addition, the affected cellular pathways, the mutated genes and the metastatic properties of the tumors are not the same. This review addresses another specificity of melanomas: the role of photo‐oxidative stress. UVA efficiently produces reactive oxygen species in melanocytes, which results in more frequent oxidatively generated DNA lesions than in other cell types. The question of the respective contribution of UVB‐induced pyrimidine dimers and UVA‐mediated oxidatively generated lesions to mutagenesis in melanoma remains open. Recent results based on next‐generation sequencing techniques strongly suggest that the mutational signature associated with pyrimidine dimers is overwhelming in melanomas like in skin carcinomas. UVA‐induced oxidative stress may yet be indirectly linked to the genotoxic pathways involved in melanoma through its ability to hamper DNA repair activities.