Silver ions enhance UVB-induced phosphorylation of histone H2AX.
Silver (Ag) is used in a wide range of industries including healthcare, food, cosmetics, and environmental industries due to its antibacterial properties. The rapidly expanding use of Ag has raised issues concerning its toxicity in humans. However, studies investigating the effects of Ag on humans are very limited, and the combined effects of Ag and other environmental factors have not yet been determined. Ultraviolet (UV) radiation in sunlight is the most prominent and ubiquitous physical stressor in our natural environment. In this study, we investigated the genotoxic potential of combined exposure to Ag(+) (AgNO3) and UVB in the human keratinocyte cell line, HaCaT, by measuring the generation of phosphorylated histone H2AX, which is currently attracting attention as a biomarker for the detection of genotoxic insults. We found that the generation of γ-H2AX was synergistically enhanced when cells were coexposed to Ag(+) and UVB. Furthermore, we showed that the enhanced generation of γ-H2AX could be attributed to the increased formation of UVB-induced cyclobutane pyrimidine dimers and (6-4) photoproducts. These lesions, if not repaired properly, are the major causal factor for skin carcinogenesis. Our results provide an important insight into influence of Ag on the genotoxic potency of sunlight.
Graduate Division of Nutritional and Environmental Sciences, University of Shizuoka, Shizuoka-Shi, Shizuoka, Japan.
Xiaoxu
X
Zhao
Tatsushi
T
Toyooka
Yuko
Y
Ibuki
D000900:Anti-Bacterial Agents / Q000737:chemistry; D015415:Biomarkers / Q000737:chemistry; D002453:Cell Cycle; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D002474:Cell-Free System; D053903:DNA Breaks, Double-Stranded; D005434:Flow Cytometry; D006657:Histones / Q000737:chemistry*; D006801:Humans; D007477:Ions; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects / Q000528:radiation effects; D009153:Mutagens / Q000737:chemistry; D010766:Phosphorylation; D011740:Pyrimidine Dimers / Q000737:chemistry; D011743:Pyrimidines / Q000737:chemistry; D012834:Silver / Q000737:chemistry*; D012878:Skin Neoplasms / Q000517:prevention & control; D013472:Sunlight; D014466:Ultraviolet Rays
D000900:Anti-Bacterial Agents; D015415:Biomarkers; C468783:H2AX protein, human; D006657:Histones; D007477:Ions; D009153:Mutagens; D011740:Pyrimidine Dimers; D011743:Pyrimidines; D012834:Silver; C030986:pyrimidine
DNA double strand breaks; UVB; histone H2AX; pyrimidine dimers; silver ion