FORMATION OF DNA ADDUCTS IN THE SKIN OF PSORIASIS PATIENTS, IN HUMAN SKIN IN ORGAN-CULTURE, AND IN MOUSE SKIN AND LUNG FOLLOWING TOPICAL APPLICATION OF COAL-TAR AND JUNIPER TAR

Preparations of coal-tar and juniper tar (cade oil) that are used in the treatment of psoriasis are known to contain numerous potentially carcinogenic polycyclic aromatic hydrocarbons (PAH). Evidence of covalent binding to DNA by components of these mixtures was sought in a) human skin biopsy samples from 12 psoriasis patients receiving therapy with these agents, b) human skin explants maintained in organ culture and treated topically with the tars, and c) the skin and lungs of mice treated with repeated doses of the formulations following the regimen used in the clinic. DNA was isolated from the human and mouse tissues and digested enzymically to mononucleotides. 32P-Post-labeling analysis revealed the presence of aromatic DNA adducts in the biopsy samples at levels of up to 0.4 fmol total adducts/μg DNA. Treatment of human skin in organ culture produced similar levels of ad ducts, while treatment with dithranol, a non-mutagenic therapeutic agent, resulted in chromatograms indistinguishable from those from untreated controls. In mouse skin, coaltar ointment and juniper tar gave similar DNA adduct levels, with a similar time-course of removal: maximum levels (0.5 fmol/μg DNA) at 24 h after the final treatment declined rapidly to 0.05 fmol/μg at 7 d, thereafter declining slowly over the succeeding 25 d. However, while coal-tar ointment produced only very low levels of adducts in mouse lung (< 0.03 fmol/μg DNA), juniper tar produced adducts at a high level (0.7 fmol/μg DNA) that were persistent in this tissue. These results provide direct evidence for the formation of potentially carcinogenic DNA damage in human and mouse tissue by components of these therapeutic tar preparations. © 1990.