The in situ repair kinetics of epidermal thymine dimers and 6-4 photoproducts in human skin types I and II.

The in situ repair kinetics of epidermal thymine dimers and 6-4 photoproducts in human skin types I and II.
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表皮胸腺嘧啶二聚体和 6-4 光产物在 I 型和 II 型人类皮肤中的原位修复动力学。

DOI:
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发表时间:
1996
影响因子:
6.5
通讯作者:
Christopher S. Potten
Christopher S. Potten
中科院分区:
医学1区
文献类型:
--
作者:
Antony R. Young;C. Chadwick;G. I. Harrison;J.L.M. Hawk;Osamu Nikaido;Christopher S. Potten

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我们评估了在原位的时间依赖性损失的表皮胸腺嘧啶二聚体和6-4 photoproducts在皮肤类型I和II暴露后,两个最小红斑剂量的太阳模拟辐射对以前未暴露的皮肤。使用定量图像分析,我们评价了单克隆抗体染色的活检切片。然后,我们在相同的志愿者中进行了比较,与非程序性DNA合成,这是整体切除修复的直接标志。胸腺嘧啶二聚体的去除缓慢(半衰期= 33.3小时),照射后24小时仍存在高水平的病变; 7天仍存在一些病变。相比之下,6-4光产物的去除是快速的(半衰期= 2.3小时),其衰减动力学与表皮非程序性DNA合成的下降(半衰期= 7.1小时)相关性更好。这些数据表明,在小鼠、猴和体外模型中,6-4光损伤优先在人表皮原位修复。他们还提出了一种可能性,即胸腺嘧啶二聚体修复不良可能是I型和II型皮肤的一个特征,他们比III型和IV型更容易患皮肤癌。红斑的发作和6-4光产物修复之间存在反比关系,表明该修复过程启动红斑。
We assessed the in situ time-dependent loss of epidermal thymine dimers and 6-4 photoproducts in skin types I and II after exposure to two minimal erythema doses of solar-simulating radiation on previously unexposed buttock skin. Using quantitative image analysis, we evaluated biopsy sections stained with monoclonal antibodies. We then made comparisons, in the same volunteers, with unscheduled DNA synthesis, which is a direct marker of overall excision repair. Removal of thymine dimers was slow (half-life = 33.3 h), with high levels of lesions still present 24 h post-irradiation; some lesions were still present at 7 d. In contrast, removal of 6-4 photoproducts was rapid (half-life = 2.3 h), the decay kinetics of which correlated better with the decline in epidermal unscheduled DNA synthesis (half-life = 7.1 h). These data show that as in mouse, monkey, and in vitro models, the 6-4 photolesion is repaired preferentially in human epidermis in situ. They also raise the possibility that poor thymine dimer repair may be a feature of skin types I and II, who are more prone to skin cancer than are types III and IV. There was an inverse relationship between the onset of erythema and 6-4 photoproduct repair, suggesting that this repair process initiates erythema.
小鼠皮肤中嘧啶(6-4)嘧啶酮光产物的修复。
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