title: Short- and long-wave UV light (UVB and UVA) induce similar mutations in human skin cells.
abstract: While the mutagenic and carcinogenic properties of longwave UV light (UVA) are well established, mechanisms of UVA mutagenesis remain a matter of debate. To elucidate the mechanisms of mutation formation with UVA in human skin, we determined the spectra of UVA- and UVB-induced mutations in primary human fibroblasts. As with UVB, we found the majority of mutations to be C-to-T transitions also with UVA. For both UVA and UVB, these transitions were found within runs of pyrimidines, at identical hotspots, and with the same predilection for the nontranscribed strand. They also included CC-to-TT tandem mutations. Therefore, these mutations point to a major role of pyrimidine dimers not only in UVB but also in UVA mutagenesis. While some differences were noted, the similarity between the spectra of UVA- and UVB-induced mutations further supports similar mechanisms of mutation formation. A non-dimer type of DNA damage does not appear to play a major role in either UVA or UVB mutagenesis. Therefore, the previously reported increasing mutagenicity per dimer with increasing wavelengths cannot be due to non-dimer DNA damage. Differences in the cellular response to UVA and UVB, such as the less prominent activation of p53 by UVA, might determine a different mutagenic outcome of UVA- and UVB-induced dimers.
authors.affiliation: Department of Dermatology, Boston University School of Medicine, Boston, Massachusetts 02118, USA.
authors.forename: Ulrike P
authors.initials: UP
authors.lastname: Kappes
authors.forename: Dan
authors.initials: D
authors.lastname: Luo
authors.forename: Marisa
authors.initials: M
authors.lastname: Potter
authors.forename: Karl
authors.initials: K
authors.lastname: Schulmeister
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Rünger
mesh_terms: D001483:Base Sequence; D002460:Cell Line; D004249:DNA Damage; D016158:Genes, p53; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D011740:Pyrimidine Dimers / Q000378:metabolism; D012867:Skin / Q000528:radiation effects*; D014466:Ultraviolet Rays
chemical_list: D011740:Pyrimidine Dimers