title: Nucleotide Excision Repair and Vitamin D--Relevance for Skin Cancer Therapy.
abstract: Ultraviolet (UV) radiation is involved in almost all skin cancer cases, but on the other hand, it stimulates the production of pre-vitamin D3, whose active metabolite, 1,25-dihydroxyvitamin D3 (1,25VD3), plays important physiological functions on binding with its receptor (vitamin D receptor, VDR). UV-induced DNA damages in the form of cyclobutane pyrimidine dimers or (6-4)-pyrimidine-pyrimidone photoproducts are frequently found in skin cancer and its precursors. Therefore, removing these lesions is essential for the prevention of skin cancer. As UV-induced DNA damages are repaired by nucleotide excision repair (NER), the interaction of 1,25VD3 with NER components can be important for skin cancer transformation. Several studies show that 1,25VD3 protects DNA against damage induced by UV, but the exact mechanism of this protection is not completely clear. 1,25VD3 was also shown to affect cell cycle regulation and apoptosis in several signaling pathways, so it can be considered as a potential modulator of the cellular DNA damage response, which is crucial for mutagenesis and cancer transformation. 1,25VD3 was shown to affect DNA repair and potentially NER through decreasing nitrosylation of DNA repair enzymes by NO overproduction by UV, but other mechanisms of the interaction between 1,25VD3 and NER machinery also are suggested. Therefore, the array of NER gene functioning could be analyzed and an appropriate amount of 1.25VD3 could be recommended to decrease UV-induced DNA damage important for skin cancer transformation.
authors.affiliation: Department of Orthodontics, Medical University of Lodz, 92-216 Lodz, Poland. elzbieta.pawlowska@umed.lodz.pl.
authors.forename: Elzbieta
authors.initials: E
authors.lastname: Pawlowska
authors.affiliation: Department of Molecular Genetics, University of Lodz, 90-236 Lodz, Poland. dwysokinski@biol.uni.lodz.pl.
authors.forename: Daniel
authors.initials: D
authors.lastname: Wysokinski
authors.affiliation: Department of Molecular Genetics, University of Lodz, 90-236 Lodz, Poland. jblasiak@biol.uni.lodz.pl.
authors.forename: Janusz
authors.initials: J
authors.lastname: Blasiak
mesh_terms: D000818:Animals; D004249:DNA Damage / Q000187:drug effects / Q000528:radiation effects; D004260:DNA Repair / Q000187:drug effects*; D006801:Humans; D008545:Melanoma / Q000209:etiology / Q000235:genetics / Q000517:prevention & control / Q000628:therapy*; D011740:Pyrimidine Dimers / Q000235:genetics; D012867:Skin / Q000187:drug effects / Q000473:pathology / Q000528:radiation effects; D012878:Skin Neoplasms / Q000209:etiology / Q000235:genetics / Q000517:prevention & control / Q000628:therapy*; D014466:Ultraviolet Rays / Q000009:adverse effects; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D014815:Vitamins / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D011740:Pyrimidine Dimers; D014815:Vitamins; C118756:dihydroxy-vitamin D3; C058406:pyrimidine-pyrimidone dimer; D014807:Vitamin D
keywords: DNA damage; DNA repair; UV radiation; melanoma; nucleotide excision repair; skin cancer