Thielmann H W, Edler L, Burkhardt M R, Jung E G
J Cancer Res Clin Oncol. 1987;113(2):171-86. doi: 10.1007/BF00391441.
Fibroblast strains derived from skin biopsies of patients with actinic keratosis (6), malignant melanoma (18), squamous cell carcinoma (11), and basal cell carcinoma (12) were investigated for DNA repair synthesis, with 16 fibroblast strains for normal donors as controls. Cells were exposed to UV light, the "UV-like" carcinogen (Ac)2ONFln, and the methylating carcinogens MeSO2OMe and MeNOUr. Dose-response experiments, which included 10 dose levels, were performed, the data analyzed by linear regression, and the slope of the regression line (term: G0) used as a measure of DNA repair synthesis. The mean experimental variability of G0 of individual fibroblast strains was 9.5%-15.4%, depending upon exposure. For comparison of all cell strains belonging to the same skin malignancy group with those of the control group, G0 values of the individual strains were combined to yield group-specific weighted mean G0 values. In addition, the capacity to incise UV-damaged DNA was measured in 24 cell strains from patients with skin tumors using the alkaline elution technique. For quantitating DNA-incising capacity, the initial velocities of the elution curves were plotted versus the UV dose, and the slope of the resulting regression line was used to obtain the characteristic value E0. The mean experimental variability of E0 of individual strains was +/- 22%. These E0 values were combined to yield weighted mean values of groups. The fibroblast strains in the groups of patients with actinic keratosis and malignant melanoma were found to have normal mean G0 values when DNA repair synthesis was challenged with UV light or one of the three carcinogens. However, the squamous cell carcinoma group exhibited significantly lower mean G0 values after treatment with UV light (82% that of normal donors), (Ac)2ONFln (70%), MeSO2OMe (70%), and MeNOUr (69%). The basal cell carcinoma group showed significantly diminished repair synthesis upon treatment with UV light (81% that of normal donors) and MeSO2OMe (67%). In contrast to these findings, in no skin malignancy group was post UV DNA-incising capacity (E0) significantly diminished, although it should be noted that group sizes were only half as large as for G0 determinations. These data may be interpreted as indicating that DNA excision repair is impaired in fibroblast strains from patients with squamous cell carcinoma and-to a lesser extent-basal cell carcinoma.(ABSTRACT TRUNCATED AT 400 WORDS)
对源自光化性角化病患者（6例）、恶性黑色素瘤患者（18例）、鳞状细胞癌患者（11例）和基底细胞癌患者（12例）皮肤活检的成纤维细胞株进行了DNA修复合成研究，以16例正常供体的成纤维细胞株作为对照。将细胞暴露于紫外线、“类紫外线”致癌物(Ac)2ONFln以及甲基化致癌物MeSO2OMe和MeNOUr。进行了包括10个剂量水平的剂量反应实验，对数据进行线性回归分析，并将回归线的斜率（术语：G0）用作DNA修复合成的指标。根据暴露情况，单个成纤维细胞株G0的平均实验变异性为9.5%-15.4%。为了将属于同一皮肤恶性肿瘤组的所有细胞株与对照组进行比较，将各个细胞株的G0值合并，得出组特异性加权平均G0值。此外，使用碱性洗脱技术在24例皮肤肿瘤患者的细胞株中测量了切割紫外线损伤DNA的能力。为了定量DNA切割能力，将洗脱曲线的初始速度与紫外线剂量作图，并使用所得回归线的斜率获得特征值E0。单个细胞株E0的平均实验变异性为±22%。将这些E0值合并得出各组的加权平均值。当用紫外线或三种致癌物之一刺激DNA修复合成时，发现光化性角化病和恶性黑色素瘤患者组中的成纤维细胞株具有正常的平均G0值。然而，鳞状细胞癌组在用紫外线（正常供体的82%）、(Ac)2ONFln（70%）、MeSO2OMe（70%）和MeNOUr（69%）处理后，平均G0值显著降低。基底细胞癌组在用紫外线（正常供体的81%）和MeSO2OMe（67%）处理后，修复合成明显减少。与这些发现相反，在任何皮肤恶性肿瘤组中，紫外线照射后的DNA切割能力（E0）均未显著降低，不过应当指出，组规模仅为G0测定时的一半。这些数据可以解释为表明鳞状细胞癌患者以及程度较轻的基底细胞癌患者的成纤维细胞株中的DNA切除修复受损。（摘要截短至40
