Human in vitro skin permeation rates for polycyclic aromatic hydrocarbons (PAHs) are altered with co-exposures to solar ultraviolet radiation (UVs)

摘要

Road construction workers are simultaneously exposed to two carcinogens; solar ultraviolet (UV) radiation and polycyclic aromatic hydrocarbons (PAHs) in bitumen emissions. The combined impact of the two carcinogens may contribute to an increased risk for skin cancer due to photogenotoxicity and enhanced PAH skin permeation rates. AIM: Our aims were to compare skin permeation rates for selected PAHs with and without simultaneous UV exposures, and to explore two possible photogenotoxicity biomarkers in vitro: p53 for DNA damage and matrix metalloproteinase-1 (MMP1) for degeneration of dermal extracellular matrix. METHOD: We used flow-through diffusion cells mounted with human viable skin (not previously frozen) to measure permeation rates over 24 hours for five PAHs; naphthalene, chrysene, anthracene, pyrene, and benzo(a)pyrene (BaP) in a mixture (5 mg/ml of each) with co-exposure to solar UV radiation (equivalent to a day of sun exposure - 600 J/m2) generated by a solar simulator (Solar Light LS1000). Human skin was obtained from abdominoplasty surgery patients (N=3) after informed consent (DAL biobank). MMP1 was determined by real time PCR and p53 by histology. RESULTS: Naphthalene, pyrene, and BaP in the PAH mixture permeated human skin greater without compared to with simultaneous exposures to UVs (13.3 vs 6.7 ng/cm2 for naphthalene, 3.32 vs 2.77 ng/cm2 pyrene, and 0.94 and 0.34 ng/cm2 for BaP, respectively). Time until breakthrough (Tlags) were similar for naphthalene (4-5h) and pyrene (7-8h) co-exposed or not to UVs; while rapid (1h) without UVs and longer (3h) with UVs for BaP. Anthracene and chrysene permeated skin to a greater extent with simultaneous exposures to UVs compared to without (1.76 vs 2.89 ng/cm2 for anthracene and 0.49 vs 0.73 ng/cm2 for chrysene, respectively). UV co-exposure did not change the Tlags for anthracene (7h) and chrysene (1h). Permeation rates increased for anthracene and chrysene; and decreased for naphthalene, pyrene, and BaP. Possible explanations are that i) skin metabolizes PAHs thus the sum of the parent compound and metabolites should be measured or ii) UVs reacts with PAHs which undergo radical reactions producing reaction products. MMP1 could not be determined due to insufficient RNA. Qualitative interpretation of p53 indicated greater damage after simultaneous exposure to PAHs and solar UV compared to either exposures separately. CONCLUSION: All PAHs measured had permeation rates between 0.34 and 13.3 ng/cm2 and permeated skin within 1-7h. Co-exposures to UVs altered PAHs skin permeation rates and could potentially increase DNA damage.