Benzo[a]pyrene and UV light co-exposure: differential effects on oxidative stress and genotoxicity in human keratinocytes and ex vivo skin.

Human skin exposure to environmental/occupational UV irradiation and polycyclic aromatic hydrocarbons (PAHs) is a concern. This study investigated the impact of the combined exposure on metabolism, cytotoxicity/viability, oxidative stress, and genotoxicity in human skin models. To understand the dose-response relationship, we exposed our models to a range of benzo[a]pyrene (B[a]P) concentrations. For the combined exposure scenario, the models were treated with B[a]P followed by UV irradiation. Furthermore, we employed two in vitro models: human keratinocytes and human skin explants. This allowed us to assess potential model-dependent variations in the observed toxicological effects. Keratinocytes displayed a partially synergistic response in most measured parameters at 0.4 µM B[a]P or higher after combined exposure. The comet assay identified significant DNA damage solely due to UV irradiation, and this damage was not further increased by combined exposure. Conversely, H2AX phosphorylation showed a dose-dependent increase in response to the combined exposure. Human skin explants displayed minimal changes in oxidative stress markers compared to keratinocytes. Additionally, DNA damage in explants was significantly reduced following UV irradiation alone and remained lower than after single B[a]P exposure, even with combined exposure. These findings suggest a potential UV-induced protective mechanism in ex vivo human skin under these conditions. Furthermore, they highlight the differential response of the models, with explants exhibiting lower reactivity due to their inherent complexity and robustness, potentially reflecting the protective mechanisms present in live skin.