Azathioprine treatment photosensitizes human skin to ultraviolet A radiation
Azathioprine treatment photosensitizes human skin to ultraviolet A radiation
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DOI：
10.1111/j.1365-2133.2008.08610.x
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发表时间：
2008-07-01
影响因子：
10.3
通讯作者：
McGregor, J. M.
中科院分区：
文献类型：
--
作者：
Perrett, C. M.;Walker, S. L.;McGregor, J. M.
硫唑嘌呤被用于治疗多种疾病和预防器官移植受者（OTRs）的移植排斥反应。目的临床研究我们以前的发现，硫唑嘌呤代谢物与紫外线（UV）A辐射相互作用，形成前致突变的氧化DNA损伤，并确定这是否可能是导致或促进皮肤癌后过量皮肤癌的发展。方法对这些资料进行临床分析。五名患者被招募和UVB，UVA和太阳模拟辐射（SSR）的最小红斑剂量（MED）确定为每个人之前，至少12周后，开始硫唑嘌呤therapy.Results在所有五名患者硫唑嘌呤治疗与UVA和SSR的皮肤敏感性增加，并显着减少UVA和SSR的MED。我们没有发现UVB诱导的红斑或MED的变化。此外，我们发现，从患者的皮肤DNA上硫唑嘌呤含有6-硫鸟嘌呤（6-TG）。结论我们的研究结果证实了DNA 6-TG的存在，在那些服用治疗剂量的硫唑嘌呤的皮肤和DNA 6-TG与UVA相互作用时发生DNA损伤，导致异常的皮肤光敏性的假设提供支持。
Background Azathioprine is used to treat a variety of conditions and to prevent graft rejection in organ transplant recipients (OTRs).Objectives To investigate clinically our previous finding that azathioprine metabolites interact with ultraviolet (UV) A radiation to form promutagenic oxidative DNA damage and to determine whether this may be causal or contributory to the development of excess skin cancers post-transplantation.Methods The clinical corollary of these data were investigated. Five patients were recruited and the minimal erythema dose (MED) for UVB, UVA and solar-simulated radiation (SSR) was determined for each person before, and at least 12 weeks after, starting azathioprine therapy.Results In all five patients azathioprine treatment was associated with an increased UVA and SSR sensitivity of the skin and a significant reduction in MEDs for UVA and SSR. We found no change in UVB-induced erythema or MED. In addition, we found that DNA from the skin of patients on azathioprine contains 6-thioguanine (6-TG).Conclusions Our findings confirm the presence of DNA 6-TG in the skin of those taking therapeutic doses of azathioprine and provide support for the hypothesis that DNA damage occurs when DNA 6-TG interacts with UVA, resulting in abnormal cutaneous photosensitivity.