title: UVA1 induces cyclobutane pyrimidine dimers but not 6-4 photoproducts in human skin in vivo.
abstract: UVB readily induces cyclobutane pyrimidine dimers, mainly thymine dimers (TTs), and pyrimidine (6-4) pyrimidone photoproducts (6-4PPs) in DNA. These lesions result in "UVB signature mutations" found in skin cancers. We have investigated the induction of TTs and 6-4PPs in human skin in vivo by broadband UVA1, and have compared this with comparable erythemal doses of monochromatic UVB (300 nm). In vitro and ex vivo studies have shown the production of TTs, without 6-4PPs, by UVA1. We show that UVA1 induces TTs, without 6-4PPs, in the epidermis of healthy volunteers in vivo, whereas UVB induced both photoproducts. UVB induced more TTs than UVA1 for the same level of erythema. The level of UVA1-induced TTs increased with epidermal depth in contrast to a decrease that was seen with UVB. UVA1- and UVB-induced TTs were repaired in epidermal cells at a similar rate. The mechanism by which UVA1 induces TTs is unknown, but a lack of intra-individual correlation between our subjects' UVB and UVA1 minimal erythema doses implies that UVA1 and UVB erythema occur by different mechanisms. Our data suggest that UVA1 may be more carcinogenic than has previously been thought.
authors: St John's Institute of Dermatology, Division of Genetics and Molecular Medicine, King's College London School of Medicine, King's College London, London, UK. angela.tewari@kcl.ac.uk
authors: Angela
authors: A
authors: Tewari
authors: Robert P
authors: RP
authors: Sarkany
authors: Antony R
authors: AR
authors: Young
mesh_terms: D004260:DNA Repair; D004307:Dose-Response Relationship, Radiation; D004890:Erythema / Q000209:etiology; D006801:Humans; D009381:Neoplasms, Radiation-Induced / Q000209:etiology; D011740:Pyrimidine Dimers / Q000032:analysis / Q000096:biosynthesis*; D012867:Skin / Q000378:metabolism / Q000528:radiation effects*; D012878:Skin Neoplasms / Q000209:etiology; D014466:Ultraviolet Rays / Q000009:adverse effects*
chemical_list: D011740:Pyrimidine Dimers; C058406:pyrimidine-pyrimidone dimer