DNA adducts in skin biopsies and 1-hydroxypyrene in urine of psoriasis patients and healthy volunteers following treatment with coal tar

• Published in: Toxicology letters Vol. 213; no. 1; pp. 39 - 44
• Main Authors: Roelofzen, J.H.J., van der Valk, P.G.M., Godschalk, R., Dettbarn, G., Seidel, A., Golsteijn, L., Anzion, R., Aben, K.K.H., van Schooten, F.J., Kiemeney, L.A.L.M., Scheepers, P.T.J.
• Format: Journal Article Conference Proceeding
• Language: English
• Published: Shannon Elsevier Ireland Ltd 13.08.2012; Elsevier
• Subjects: 1-Hydroxypyrene; absorption; Adolescent; Adult; Aged; bioavailability; Biological and medical sciences; Biomarkers; Biopsy; Carcinogenesis, carcinogens and anticarcinogens; Carcinogenic effect; carcinogenicity; Case-Control Studies; Chemical agents; coal; Coal tar; Coal Tar - adverse effects; Coal Tar - pharmacokinetics; Coal Tar - therapeutic use; Dermatology; DNA adducts; DNA Adducts - analysis; Drug toxicity and drugs side effects treatment; eczema; excretion; exposure duration; Humans; Male; males; Medical sciences; metabolism; Middle Aged; nucleotides; ointments; PAH-DNA adducts; patients; Pharmacology. Drug treatments; polycyclic aromatic hydrocarbons; psoriasis; Psoriasis - drug therapy; Psoriasis - metabolism; Psoriasis. Parapsoriasis. Lichen; Pyrenes - analysis; risk; Skin - chemistry; Toxicity: skin, dermoskeleton; Tumors; urine; volunteers; Young Adult; Biomarkers; PAH-DNA adducts; Coal tar; 1-Hydroxypyrene; Carcinogenic effect; Human; Urine; Biological fluid; Skin disease; Healthy subject; Psoriasis; Biological marker; Polycyclic aromatic compound; Carcinogen; Anatomic pathology; Treatment; Biopsy; DNA; Skin; Molecular adduct
• ISSN: 0378-4274; 1879-3169; 1879-3169
• DOI: 10.1016/j.toxlet.2011.06.030

► Coal tar ointments contain several carcinogenic polycyclic aromatic hydrocarbons ► Urinary 1-OHP levels and PAH-DNA adducts were studied after coal tar application ► Patients with psoriasis were compared to skin of healthy volunteers ► Biomarkers for uptake and activation of PAH were lower in patients than in volunteers. Coal tar ointments (CTO) are frequently used in the treatment of psoriasis and eczema, but CTO contain carcinogenic polycyclic aromatic hydrocarbons (PAH). PAH are absorbed and metabolized in the skin. In psoriasis, the skin barrier is altered and therefore, absorption and metabolism of PAH may differ from healthy skin. In this study, levels of urinary 1-hydroxypyrene and PAH-DNA adducts in the skin were studied in psoriatic patients and healthy volunteers. Three punch biopsies were taken from the lower back of 10 male volunteers and from a psoriatic plaque in 10 male patients. A surface of 6.25cm2 was treated with CTO. After 96h CTO was removed and another three skin biopsies were collected from the treated area. DNA was isolated from skin biopsies and urine was collected during and after the exposure period. After 24h, a twofold lower 1-hydroxypyrene urinary excretion was observed in patients compared to healthy volunteers and after 48h, this difference reached statistical significance (p<0.05). Over 96h the median level of the sum of PAH-DNA adducts, analyzed by 32P-post-labeling, increased from 3.5 before CTO administration to 21.1 adducts per 108 nucleotides in volunteers, and from 1.0 to 3.6 adducts per 108 nucleotides in patients. At 96h, PAH-DNA levels were higher in healthy volunteers than in patients (p<0.05). Biomarkers for uptake, bioavailability and bioactivation of PAH were lower in patients compared to volunteers. These data suggest a lower risk of carcinogenic effects of CTO in psoriatic skin compared to healthy skin.