Toxicology Letters 213 (2012) 39–44 Contents lists available at ScienceDirect Toxicology Letters jou rn al h om epage: www.elsevier.com/locate/toxlet DNA adducts in skin biopsies and 1-hydroxypyrene in urine of psoriasis patients and healthy volunteers following treatment with coal tar J.H.J. Roelofzen a,∗ , P.G.M. van der Valk a , R. Godschalk b , G. Dettbarn c , A. Seidel c , L. Golsteijn d , R. Anzion d , K.K.H. Aben d,e , F.J. van Schooten b , L.A.L.M. Kiemeney d,e , P.T.J. Scheepers d a Department of Dermatology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands b Department of Health Risk Analysis and Toxicology, School of Nutrition, Toxicology and Metabolism, Maastricht University, The Netherlands c Biochemical Institute for Environmental Carcinogens, Prof. Dr. Gernot Grimmer-Foundation, Grosshansdorf, Germany d Department of Epidemiology, Biostatistics and HTA, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands e Comprehensive Cancer Centre East (IKO), Nijmegen, The Netherlands a r t i c l e i n f o Article history: Available online 23 July 2011 Keywords: Coal tar 1-Hydroxypyrene PAH-DNA adducts Biomarkers Carcinogenic effect a b s t r a c t 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 6.25 cm 2 was treated with CTO. After 96 h 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 24 h, a twofold lower 1-hydroxypyrene urinary excretion was observed in patients compared to healthy volunteers and after 48 h, this difference reached statistical significance (p < 0.05). Over 96 h the median level of the sum of PAH-DNA adducts, analyzed by 32 P-post-labeling, increased from 3.5 before CTO administration to 21.1 adducts per 10 8 nucleotides in volunteers, and from 1.0 to 3.6 adducts per 10 8 nucleotides in patients. At 96 h, 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. © 2011 Elsevier Ireland Ltd. All rights reserved. 1. Introduction Coal tar is one of the oldest topical treatments in dermatol- ogy. Nowadays, it is still used by dermatologist in the treatment of eczema and psoriasis (Roelofzen et al., 2007). It contains more than 10,000 compounds, including polycyclic aromatic hydrocar- bons (PAH) in high concentrations (Scheepers et al., 2009). Some PAH, such as benzo(a)pyrene are classified as human carcinogens (IARC, 2010), based on both animal studies (Boffetta et al., 1997; IARC, 1985; Marston et al., 2001) and occupational studies (Donato et al., 2000; IARC, 1985; Partanen and Boffetta, 1994; Tsai et al., ∗ Corresponding author at: Department of Dermatology, Radboud University Nijmegen Medical Centre, P.O. Box 9101, 6500 HB Nijmegen, the Netherlands. Tel.: +31 243613247; fax: +31 243610780. E-mail address: J.Roelofzen@derma.umcn.nl (J.H.J. Roelofzen). 2001), that demonstrated associations between PAH exposure and lung, skin and bladder cancer. Surprisingly, only few studies have investigated the iatrogenic risk of cancer in patients treated with coal tar. Moreover, the majority of these studies did not observe an increased risk of cancer (Hannuksela-Svahn et al., 2000; Jones et al., 1985; Larko and Swanbeck, 1982; Maughan et al., 1980; Pittelkow et al., 1981). Only Stern et al. found an increased risk of non- melanoma skin cancer in patients treated with coal tar (Stern et al., 1980). Recently, we performed a large historical cohort study in 13,000 patients with psoriasis and eczema to study the risk of can- cer after dermatological treatment with coal tar ointments (CTO) (Roelofzen et al., 2010a). This study showed that treatment with coal tar did not increase the risk of squamous cell or melanoma skin cancer, nor the risk of non-skin malignancies. Differences in cancer risks observed in occupational studies versus studies in patients may be explained by the frequency, level and duration of PAH exposure. Malignancies have occurred after 0378-4274/$ – see front matter © 2011 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.toxlet.2011.06.030