Ultraviolet A light is commonly emitted by UV-nail polish dryers with recent reports suggesting that long-term use may increase the risk for developing skin cancer. However, no experimental evaluation has been conducted to reveal the effect of radiation emitted by UV-nail polish dryers on mammalian cells. Here, we show that irradiation by a UV-nail polish dryer causes high levels of reactive oxygen species, consistent with 8-oxo-7,8-dihydroguanine damage and mitochondrial dysfunction. Analysis of somatic mutations reveals a dose-dependent increase of C:G>A:T substitutions in irradiated samples with mutagenic patterns similar to mutational signatures previously attributed to reactive oxygen species. In summary, this study demonstrates that radiation emitted by UV-nail polish dryers can both damage DNA and permanently engrave mutations on the genomes of primary mouse embryonic fibroblasts, human foreskin fibroblasts, and human epidermal keratinocytes.

Abstract: Ultraviolet A (UVA) rays are long wavelengths that can penetrate the deeper layer of the skin and are responsible for the immediate tanning effect. A multitude of natural and artificial sources of UV exposure exist, including UV-emitting lamps that are commonly used in dentistry, cosmetics, and medical laboratories. Recently, several reports suggested that long-term use of UV-nail polish dryers, used for curating nail polish formulas, known as gel, may increase the risk for developing skin cancer. However, no experimental evaluation has been conducted to reveal the effect of radiation released by UV-nail polish dryers on mammalian cells. Here, we address the continuous exposure of clients and employees to UVA light by employing both murine and human primary cell models for irradiation, in an acute and chronic manner, using a UV-dryer machine. We, then, subject the cells to DNA sequencing either by bulk whole-genome sequencing after clonal expansion or by single-molecule duplex sequencing without clonal expansion. Our findings show that UVA-exposed samples manifest an increase of C:G>A:T transversions compared to control cells. The patterns of mutations found in these cells can be recapitulated by mutational signatures previously attributed to reactive oxygen species (ROS), namely COSMIC signatures SBS18/36. These results are further corroborated by the presence of high levels of ROS in irradiated samples, consistent with 8-oxo-7,8-dihydroguanine damage and mitochondrial dysfunction. Importantly, we show that in contrast to UVB exposure, UVA does not induce an increase of C:G>T:A transitions, indicating that different types of ultraviolet light radiation affect DNA through distinctive molecular mechanisms. Finally, re-examination of somatic mutations from skin cancers reported by the International Cancer Genome Consortium (ICGC) reveals that SBS18/36 are ubiquitously present in melanoma and account for 12% of the previously annotated driver mutations. In summary, this study demonstrates that radiation emitted by UV-nail polish dryers can both damage DNA and permanently engrave mutations on the genomes of mammalian cells. Citation Format: Maria Zhivagui, Areebah Hoda, Noelia Valenzuela, Yi-yu Yeh, Jason Dai, Yudou He, Shuvro P. Nandi, Burcak Otlu, Bennett Van Houten, Ludmil Alexandrov. DNA damage and somatic mutations in mammalian cells after irradiation with a nail polish dryer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr LB059.

Mutational signature analysis is commonly performed in cancer genomic studies. Here, we present SigProfilerExtractor, an automated tool for de novo extraction of mutational signatures, and benchmark it against another 13 bioinformatics tools by using 34 scenarios encompassing 2,500 simulated signatures found in 60,000 synthetic genomes and 20,000 synthetic exomes. For simulations with 5% noise, reflecting high-quality datasets, SigProfilerExtractor outperforms other approaches by elucidating between 20% and 50% more true-positive signatures while yielding 5-fold less false-positive signatures. Applying SigProfilerExtractor to 4,643 whole-genome- and 19,184 whole-exome-sequenced cancers reveals four novel signatures. Two of the signatures are confirmed in independent cohorts, and one of these signatures is associated with tobacco smoking. In summary, this report provides a reference tool for analysis of mutational signatures, a comprehensive benchmarking of bioinformatics tools for extracting signatures, and several novel mutational signatures, including one putatively attributed to direct tobacco smoking mutagenesis in bladder tissues.