{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE336nnn/GSE336622/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Transcriptomics"],"species":["Homo sapiens"],"gds_type":["Expression profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE336622"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"Trivalent arsenicals enhance UVA-associated genomic instability in human keratinocyte models","description":"Inorganic arsenic is a well-established human carcinogen strongly associated with non-melanoma skin cancer, yet its interaction with solar radiation remains incompletely understood. Arsenic-related tumors arise preferentially in sun-exposed regions and frequently exhibit mutational patterns associated with oxidative stress rather than classical ultraviolet B signatures, implicating ultraviolet A (UVA) radiation as a potential co-exposure factor. Here, we evaluated the effects of physiologically relevant concentrations of trivalent arsenicals on UVA-associated genomic instability using keratinocyte models differing in p53 status. A multi-endpoint platform integrating comet assay kinetics, micronucleus analysis, Bliss synergy modeling, and transcriptomic profiling was used to characterize combinational responses. Sub-micromolar arsenicals alone produced minimal cytotoxicity and negligible increases in comet-detectable DNA damage. In contrast, co-exposure with UVA significantly increased chromosomal instability, particularly in p53-deficient and p53-mutant cells, despite limited additional comet signal. Repair kinetics demonstrated efficient lesion resolution in primary keratinocytes, whereas monomethylarsonous acid (MMA(III)) selectively impaired repair progression in p53-mutant HaCaT cells. Transcriptomic analysis identified altered expression of replication- and checkpoint-associated pathways in transformed keratinocytes. Across models, micronucleus formation was disproportionately elevated relative to measurable strand-break induction, indicating a dissociation between initial DNA damage and downstream genomic outcomes. Collectively, these findings support a model in which arsenicals enhance UVA-associated genomic instability by altering the processing and persistence of oxidative DNA damage rather than substantially increasing initial lesion burden.","dates":{"publication":"2026/06/30"},"accession":"GSE336622","cross_references":{"GSM":["GSM9838900","GSM9838901","GSM9838902","GSM9838903","GSM9838896","GSM9838897","GSM9838898","GSM9838899"],"GPL":["20301"],"GSE":["336622"],"taxon":["Homo sapiens"]}}