UVC Irradiation Induces the Accumulation of Pentose Phosphate Pathway Metabolites and the Depletion of Glycolytic Metabolites

Background/Objectives: Ultraviolet C (UVC) disinfection devices have been widely adopted since the COVID-19 pandemic. Short UVC exposure reportedly exerts greater cytotoxicity against cancer cells than normal cells. This study examined whether this differential sensitivity is associated with rapid, cancer-cell-specific changes in intracellular metabolites. Methods: Two malignant/non-malignant cell pairs were examined: COLO 679 melanoma cells and human dermal fibroblasts (HDFa), and Ca9-22 gingival carcinoma cells and human gingival fibroblasts (HGF). Viability was assessed using the MTT assay, and metabolites extracted immediately after irradiation were quantified by capillary electrophoresis–time-of-flight mass spectrometry. Results: UVC caused a time-dependent reduction in viability that reached a plateau after 48 h. Sensitivity decreased in the following order: cancer cells, young normal cells, and normal cells at advanced population doubling levels. Baseline metabolic profiles differed markedly between malignant and non-malignant cells. UVC significantly altered 27 of 139 metabolites in Ca9-22 cells, 56 of 142 in HGF, 7 of 136 in COLO 679, and 18 of 129 in HDFa. All four cell types accumulated the pentose phosphate pathway intermediates 6-phosphogluconate and ribulose 5-phosphate, whereas the glycolytic intermediates fructose 6-phosphate, 3-phosphoglycerate, and phosphoenolpyruvate decreased. Succinate decreased in both gingiva-derived cell types. Glutathione, NAD-related metabolites, and ATP showed no marked immediate changes. Conclusions: No cancer-cell-specific metabolic response was identified. Instead, UVC induced a common pattern characterized by the accumulation of pentose phosphate pathway intermediates and the depletion of glycolytic intermediates. This pattern may reflect an early response supporting nucleotide synthesis for DNA repair that is subsequently disrupted, potentially in association with mitochondrial dysfunction.