Blue Light Aminolevulinic Acid Photodynamic Therapy Did Not Induce Detectable CPD or 6-4PP Photolesions in Human...

Photodynamic therapy (PDT) is an established dermatologic therapeutic modality used to induce apoptosis within targeted tissue. Despite increasing clinical use, the genotoxic safety of blue light (BL) PDT has not yet been established. We examined whether combination BL (417 ± 5 nm) and 5-aminolevulinic acid (5-ALA) PDT induces cyclobutane pyrimidine dimers (CPDs) and 6-4 photoproducts (6-4PPs) in human dermal fibroblasts. CRL-2617 and AG-13145 fibroblasts were treated with 0, 0.5, or 1 mM 5-ALA, then irradiated with BL at 10, 30, or 45 J/cm². Unlike robust photolesion formation in the UVB-irradiated positive controls, no BL PDT experimental condition produced CPD or 6-4PP signal exceeding the empirically validated assay lower limit of quantification (LLOQ; 1.5625 ng/mL). However, sub-LLOQ DNA damage cannot be excluded. The minimum detectable effect was 2.42 ng/mL, ~1.55-fold the LLOQ. Linear mixed-effects sensitivity analysis confirmed assay responsiveness, demonstrating clear separation between UVB and BL PDT signals.