Characterising the urinary excretion of thymidine dimer photolesions in mice

DNA damage in the form of thymidine dimers (T < > Ts) is formed in the skin in response to ultraviolet radiation (UVR). T < > Ts are excised from the skin and excreted into the urine at a quantifiable concentration. Recently, detection of T < > Ts were described in murine urine, but little is known about the excretion pattern or kinetics of T < > Ts in murine models following UVR. This study presents a characterisation of the urinary excretion of T < > Ts in hairless mice exposed to UVR. Using ultrahigh-performance liquid chromatography coupled to mass spectrometry, T < > T excretion showed a linear relationship with the UVR dose mice were exposed to, with an age-dependent decline in DNA repair capacity. Factors such as UVR exposure source and time for urine collection also impacted T < > T concentration. When applying the method to test three types of treatments for their effect on T < > T excretion, results showed an effect from sunscreen and immunosuppressants but not nicotinamide despite reports of protection. Overall, the findings demonstrate the potential of a new non-invasive method to screen drug candidates for how they affect repair of T < > Ts. Application of such a test system may advance the discovery of new treatment options to better protect against skin cancer.[GRAPHICS]