Ponten F, Lindman H, Bostrom A, Berne B, Bergh J
Department of Genetics and Pathology, University Hospital, Uppsala, Sweden.
J Natl Cancer Inst. 2001 Jan 17;93(2):128-33. doi: 10.1093/jnci/93.2.128.
p53 protein plays an important role in the response to DNA damage, and radiotherapy can cause radiation dermatitis. p53 and p21 levels increase in vitro when DNA is damaged by UVA, UVB, or gamma-radiation. To determine whether this response occurs in human skin and predicts the level of radiation dermatitis, we investigated levels of p53 and p21 in skin exposed to different types of radiation as part of a randomized study of women with breast cancer to evaluate topical steroid or emollient cream treatments for radiation dermatitis of their irradiated breast.
After surgery but before receiving tangential 5-mV photo-beam radiotherapy (2 Gy and 54 Gy) to the affected breast parenchyma, multiple areas on the backs of 50 women were irradiated with UVA and other areas were irradiated with UVB. Skin biopsy samples were taken from areas of normal unirradiated skin and all irradiated areas, and p53 and p21 were detected immunohistochemically. All statistical tests are two-sided.
In skin irradiated with UVA or UVB, medians of 4.4% (range = 0%-40.5%) or 45.5% (range = 5.3%-74.6%) p53-positive keratinocytes, respectively, were observed. Radiotherapy produced medians of 31.0% (range = 0%-79.3%) p53-immunoreactive cells after 2 Gy of radiation and 83.2% (range = 37.6%-95.2%) after 54 Gy of radiation. Despite large interindividual differences in p53 response, comparable increases in epidermal p53 response were independent of the type of radiation. A correlation between p53 and p21 was also evident (r(s) =.78). In breast skin, there was no association between the p53 response and the degree of erythema (a measure of radiation dermatitis) and no statistically significant difference between treatment arms and p21/p53 responses.
Individual responses to radiation-induced DNA damage varied widely and may be independent of the type of radiation. The epidermal p53 response does not predict the degree of radiation dermatitis.
p53蛋白在对DNA损伤的反应中起重要作用，放疗可导致放射性皮炎。当DNA受到紫外线A（UVA）、紫外线B（UVB）或γ射线损伤时，p53和p21水平在体外会升高。为了确定这种反应是否在人体皮肤中发生并预测放射性皮炎的程度，我们在一项针对乳腺癌女性的随机研究中，调查了暴露于不同类型辐射的皮肤中p53和p21的水平，该研究旨在评估局部类固醇或润肤霜治疗其受照射乳房放射性皮炎的效果。
在手术之后但在对患侧乳腺实质进行切线方向的5兆伏光子束放疗（2 Gy和54 Gy）之前，对50名女性背部的多个区域进行UVA照射，其他区域进行UVB照射。从未受照射的正常皮肤区域和所有受照射区域采集皮肤活检样本，采用免疫组织化学方法检测p53和p21。所有统计检验均为双侧检验。
在接受UVA或UVB照射的皮肤中，分别观察到p53阳性角质形成细胞的中位数为4.4%（范围 = 0% - 40.5%）或45.5%（范围 = 5.3% - 74.6%）。放疗后，2 Gy照射后p53免疫反应性细胞的中位数为31.0%（范围 = 0% - 79.3%），54 Gy照射后为83.2%（范围 = 37.6% - 95.2%）。尽管个体对p53的反应存在很大差异，但表皮p53反应的类似增加与辐射类型无关。p53和p21之间也存在明显的相关性（斯皮尔曼相关系数r(s)=.78）。在乳房皮肤中，p53反应与红斑程度（放射性皮炎的一种度量）之间没有关联，治疗组与p21/p53反应之间也没有统计学上的显著差异。
个体对辐射诱导的DNA损伤的反应差异很大，可能与辐射类型无关。表皮p53反应不能预测放射性皮炎的程度。
