Toxicity and DNA repair in normal human keratinocytes co-exposed to benzo[a]pyrene and sunlight

Anne von Koschembahr (1, 2) , Antonia Youssef (1, 2) , David Béal (1, 2) , Leslie Gudimard (1, 2) , Jean-Philippe Giot (3) , Thierry Douki (1, 4, 5, 2)

1 CIBEST - Chimie Interface Biologie pour l’Environnement, la Santé et la Toxicologie
2 DIESE - Département Interfaces pour l'énergie, la Santé et l'Environnement
3 CHUGA - Centre Hospitalier Universitaire [CHU Grenoble]
4 SYMMES - SYstèmes Moléculaires et nanoMatériaux pour l’Energie et la Santé
5 DRF (CEA) - Direction de Recherche Fondamentale (CEA)

Skin has the potential to be exposed to both solar UV radiation and polycyclic aromatic hydrocarbons, especially in occupational environments. In the present work, we investigated how benzo[a]pyrene (B[a]P) modulates cellular phototoxicity and impacts formation and repair of pyrimidine dimers induced by simulated sunlight (SSL) in normal human keratinocytes (NHK). We were especially interested in determining whether the aryl hydrocarbon receptor (AhR) was involved since it was recently shown to negatively impact repair. Addition of 1 μM B[a]P after exposure to 2 minimal erythemal doses of SSL had little impact on NHK. The inverse protocol involving incubation with B[a]P followed by irradiation led to a strong increase in phototoxicity. Repair of DNA photoproducts was drastically impaired. Using agonists and antagonists of AhR allowed us to conclude that this factor was not involved in these results. Observation of a strong increase in the level of the oxidative marker 8- oxo-7,8-dihydroguanine in the protocol involving B[a]P treatment followed by exposure to SSL strongly suggested that a photosensitized oxidative stress was responsible for cell death and inhibition of DNA repair. Accordingly, both adverse effects were diminished with a lower concentration of B[a]P and a lower SSL dose, leading to less oxidative stress.

Domaines: Biochimie [q-bio.BM]

Anne von Koschembahr, Antonia Youssef, David Béal, Leslie Gudimard, Jean-Philippe Giot, et al.. Toxicity and DNA repair in normal human keratinocytes co-exposed to benzo[a]pyrene and sunlight. Toxicology in Vitro, 2020, 63, pp.104744. ⟨10.1016/j.tiv.2019.104744⟩. ⟨hal-02417289⟩