title: G-to-T transversions and small tandem base deletions are the hallmark of mutations induced by ultraviolet a radiation in mammalian cells.
abstract: Ultraviolet A (UVA) radiation received from the sun and from the widespread use of tanning beds by populations residing in areas of northern latitude represents a potential risk factor for human health. The genotoxic and cancer-causing effects of UVA have remained controversial. A mutagenic role for UVA based on DNA damage formation by reactive oxygen species as well as by generation of photoproducts such as cyclobutane pyrimidine dimers (CPDs) has been suggested. Here, we investigated the mutagenicity of UVA in relation to its DNA damaging effects in transgenic Big Blue mouse embryonic fibroblasts. We determined the formation of a typical oxidative DNA lesion, 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxo-dG), and of CPDs, as well as quantified the induction of mutations in the cII transgene in cells irradiated with a 2000 W UVA lamp. UVA irradiation at a dose of 18 J/cm(2) produced significant levels of 8-oxo-dG in DNA (P < 0.03) but did not yield detectable CPDs. UVA irradiation also increased the cII mutant frequency almost 5-fold over background (P < 0.01) while showing moderate cytotoxicity (70% cell viability). UVA-induced mutations were characterized by statistically significant increases in G-to-T transversions and small tandem base deletions (P = 0.0075, P = 0.008, respectively) relative to spontaneously derived mutations. This mutational spectrum differs from those previously reported for UVA in other test systems; however, it corresponds well with the known spectrum of mutations established for oxidative base lesions such as 8-oxo-dG. We conclude that UVA has the potential to trigger carcinogenesis owing to its mutagenic effects mediated through oxidative DNA damage.
authors.affiliation: Division of Biology, Beckman Research Institute of the City of Hope National Medical Center, 1450 East Duarte Road, Duarte, California 91010, USA. ania@coh.org
authors.forename: Ahmad
authors.initials: A
authors.lastname: Besaratinia
authors.forename: Timothy W
authors.initials: TW
authors.lastname: Synold
authors.forename: Bixin
authors.initials: B
authors.lastname: Xi
authors.forename: Gerd P
authors.initials: GP
authors.lastname: Pfeifer
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D001483:Base Sequence; D002470:Cell Survival / Q000528:radiation effects; D004247:DNA / Q000378:metabolism / Q000528:radiation effects*; D018736:DNA Adducts / Q000032:analysis / Q000378:metabolism; D004249:DNA Damage / Q000235:genetics*; D004252:DNA Mutational Analysis; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000032:analysis / Q000378:metabolism; D043224:Deoxyribonuclease (Pyrimidine Dimer) / Q000378:metabolism; D004622:Embryo, Mammalian / Q000166:cytology; D005347:Fibroblasts / Q000528:radiation effects; D017353:Gene Deletion; D006147:Guanine; D051379:Mice; D008969:Molecular Sequence Data; D016296:Mutagenesis / Q000235:genetics*; D011740:Pyrimidine Dimers / Q000032:analysis / Q000378:metabolism; D013936:Thymidine; D014157:Transcription Factors / Q000235:genetics; D019076:Transgenes / Q000235:genetics / Q000528:radiation effects; D014466:Ultraviolet Rays / Q000009:adverse effects*; D014764:Viral Proteins / Q000378:metabolism
chemical_list: D018736:DNA Adducts; D011740:Pyrimidine Dimers; D014157:Transcription Factors; D014764:Viral Proteins; C039000:cII protein, bacteriophage lambda; D006147:Guanine; D000080242:8-Hydroxy-2'-Deoxyguanosine; D004247:DNA; C470698:endonuclease V, phage T4; D043224:Deoxyribonuclease (Pyrimidine Dimer); D003849:Deoxyguanosine; D013936:Thymidine