Photogenotoxicity of N-nitrosoproline plus simultaneous UVA irradiation in human-derived keratinocytes.

In this study, we investigated the genotoxicity of N-nitrosoproline (NPRO) in human-derived keratinocytes (HaCaT and NCTC2544 cells) using simultaneous UVA irradiation without metabolic activation. NPRO plus UVA exhibited dose- and intensity-dependent micronuclei formation in the keratinocytes, as well as nitric oxide (NO) production. The action spectra of genotoxicity and NO formation from NPRO plus UVA followed the absorption curve of NPRO, indicating that photoenergy was absorbed by the NPRO-triggered photoreaction. A significant increase in cyclic guanosine monophosphate (cGMP) was observed in HaCaT cells treated with NPRO plus UVA. NO production from UVA-irradiated NPRO paralleled micronuclei formation, and the phototoxicity of NPRO may have simultaneously interfered with the cGMP-related signaling systems caused by NO from photoactivated NPRO.