Herring C J, West C M, Wilks D P, Davidson S E, Hunter R D, Berry P, Forster G, MacKinnon J, Rafferty J A, Elder R H, Hendry J H, Margison G P
Cancer Research Campaign Section of Genome Damage and Repair, Paterson Institute for Cancer Research, Manchester, UK.
Br J Cancer. 1998 Nov;78(9):1128-33. doi: 10.1038/bjc.1998.641.
A study was made of the relationship between the intrinsic radiosensitivity of human cervical tumours and the expression of the DNA repair enzyme human apurinic/apyrimidinic endonuclease (HAP1). The radiosensitivity of clonogenic cells in tumour biopsies was measured as surviving fraction at 2 Gy (SF2) using a soft agar assay. HAP1 expression levels were determined after staining of formalin-fixed paraffin-embedded tumour sections with a rabbit antiserum raised against recombinant HAP1. Both measurements were obtained on pretreatment biopsy material. All 25 tumours examined showed positive staining for HAP1, but there was heterogeneity in the level of expression both within and between tumours. The average coefficients of variation for intra- and intertumour heterogeneity were 62% and 82% respectively. There was a moderate but significant positive correlation between the levels of HAP1 expression and SF2 (r = 0.60, P = 0.002). Hence, this study shows that there is some relationship between intrinsic radiosensitivity and expression of a DNA repair enzyme in cervical carcinomas. The results suggest that this type of approach may be useful in the development of rapid predictive tests of tumour radiosensitivity.
一项关于人类宫颈肿瘤的内在放射敏感性与DNA修复酶人脱嘌呤/脱嘧啶内切酶（HAP1）表达之间关系的研究。使用软琼脂试验，将肿瘤活检中克隆形成细胞的放射敏感性测量为2 Gy时的存活分数（SF2）。在用针对重组HAP1产生的兔抗血清对福尔马林固定石蜡包埋的肿瘤切片进行染色后，测定HAP1表达水平。这两项测量均在预处理活检材料上获得。所检查的所有25个肿瘤均显示HAP1染色阳性，但肿瘤内部和肿瘤之间的表达水平存在异质性。肿瘤内和肿瘤间异质性的平均变异系数分别为62%和82%。HAP1表达水平与SF2之间存在中等程度但显著的正相关（r = 0.60，P = 0.002）。因此，本研究表明宫颈癌的内在放射敏感性与DNA修复酶的表达之间存在一定关系。结果表明，这种方法可能有助于开发肿瘤放射敏感性的快速预测试验。
