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.
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.
复制标题
银屑病患者的皮肤、器官培养物中的人类皮肤以及局部使用煤焦油和杜松焦油后的小鼠皮肤和肺中形成 DNA 加合物。
DOI：
10.1111/1523-1747.ep12874576
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发表时间：
1990
期刊：
影响因子：
--
通讯作者：
Phillips,DH
中科院分区：
文献类型：
--
作者：
Schoket,B;Horkay,I;Kósa,A;Páldeák,L;Hewer,A;Grover,PL;Phillips,DH
已知用于治疗银屑病的煤焦油和杜松焦油（松油）制剂含有许多潜在致癌的多环芳烃（PAH）。这些混合物的组分与DNA共价结合的证据是在a）来自接受这些试剂治疗的12名银屑病患者的人皮肤活检样品，B）保持在器官培养物中并用焦油局部处理的人皮肤外植体，和c）按照临床使用的方案用重复剂量的制剂处理的小鼠的皮肤和肺中寻找的。从人和小鼠组织中分离DNA，酶消化成单核苷酸，~（32）P-后标记分析表明，在活检样品中存在芳香族DNA加合物，其含量高达0.4fmol总加合物/μ gDNA。在器官培养中处理人体皮肤产生类似水平的加合物，而用地蒽酚（一种非致突变治疗剂）处理导致与未处理对照的色谱图无法区分。在小鼠皮肤中，煤焦油软膏和杜松焦油产生了相似的DNA加合物水平，具有相似的去除时间过程：最终处理后24 h的最高水平（0.5 fmol/μg DNA）迅速下降至7 d的0.05 fmol/μg，此后在随后的25 d内缓慢下降。然而，虽然煤焦油软膏在小鼠肺中仅产生非常低水平的加合物（<0.03 fmol/μg DNA），但杜松焦油产生高水平的加合物（0.7 fmol/μg DNA），并在该组织中持续存在。这些结果提供了直接证据，证明这些治疗性焦油制剂的组分在人类和小鼠组织中形成潜在致癌的DNA损伤。
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 adducts, 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.