Oral nicotinamide mononucleotide (NMN) increases tissue NAD⁺ content in mice but neither NMN nor Polypodium leucotomos protect against UVR-induced skin cancer

Keratinocyte carcinoma is the most common cancer. Oral photoprotection offers an attractive addition to classical prevention measures. Popular candidates include nicotinamide and nicotinamide mononucleotide (NMN), which are NAD⁺ precursors thought to facilitate DNA repair. Extracts from the Polypodium leucotomos plant (PL) are also reported to convey broad protection against ultraviolet radiation (UVR) in both human and animal models. In this study, we evaluated the efficacy of NMN and PL treatment to prevent UVR-induced tumor development in hairless mice. Oral treatment with NMN or PL did not affect tumor development evaluated by tumor onset, number, size, or growth. Oral NMN increased NAD⁺ content in skin compared to the UVR control (p ≤ 0.00039) and liver tissue compared to the UVR control and non-exposed mice (p ≤ 0.0466) with no effect on tumor growth. We also demonstrated that UVR exposure induced urinary excretion of thymidine dimers in mice as measured by liquid chromatography–mass spectrometry, indicating that the induction of photodamage can be monitored non-invasively throughout the study period.