Trivalent arsenicals enhance UVA-associated genomic instability in human keratinocyte models

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.