title: DNA adducts in skin biopsies and 1-hydroxypyrene in urine of psoriasis patients and healthy volunteers following treatment with coal tar.
abstract: 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 24h, 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.
authors.affiliation: Department of Dermatology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands. J.Roelofzen@derma.umcn.nl
authors.forename: J H J
authors.initials: JH
authors.lastname: Roelofzen
authors.forename: P G M
authors.initials: PG
authors.lastname: van der Valk
authors.forename: R
authors.initials: R
authors.lastname: Godschalk
authors.forename: G
authors.initials: G
authors.lastname: Dettbarn
authors.forename: A
authors.initials: A
authors.lastname: Seidel
authors.forename: L
authors.initials: L
authors.lastname: Golsteijn
authors.forename: R
authors.initials: R
authors.lastname: Anzion
authors.forename: K K H
authors.initials: KK
authors.lastname: Aben
authors.forename: F J
authors.initials: FJ
authors.lastname: van Schooten
authors.forename: L A L M
authors.initials: LA
authors.lastname: Kiemeney
authors.forename: P T J
authors.initials: PT
authors.lastname: Scheepers
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001706:Biopsy; D016022:Case-Control Studies; D003033:Coal Tar / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use; D018736:DNA Adducts / Q000032:analysis*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011565:Psoriasis / Q000188:drug therapy* / Q000378:metabolism; D011721:Pyrenes / Q000032:analysis*; D012867:Skin / Q000737:chemistry*; D055815:Young Adult
chemical_list: D018736:DNA Adducts; D011721:Pyrenes; D003033:Coal Tar; C033146:1-hydroxypyrene