Begg A C, Russell N S, Knaken H, Lebesque J V
Department of Experiment Therapy, The Netherlands Cancer Institute, Antoni van Leeuwenhoekhuis, Amsterdam.
Int J Radiat Biol. 1993 Oct;64(4):393-405. doi: 10.1080/09553009314551581.
Fibroblasts from breast cancer patients were obtained as outgrowths in vitro from punch biopsies and their radiosensitivity tested in early passages. Skin erythema reactions in the same patients were also measured, as degree of redness using reflectance spectrophotometry. Measurements were taken before and during a 4-week radiotherapy treatment with electrons to the thoracic wall. Of 59 biopsies studied, radiosensitivity and erythema were concurrently studied in 32. In 24, evaluable data from both clinic and laboratory were obtained. A population growth assay in 96-well plates, using absorption of sulphur rhodamine B as the stain for cell numbers, showed good agreement with the colony-formation assay. Plating efficiencies and growth rates in the colony assay were higher using human serum in place of foetal calf serum. Cell survival curves with human serum were mostly exponential with little shoulder. The parameters of survival at 2 Gy (SF2) and the dose required to give 10% survival (D10) were used in the correlations with clinical data; these were 0.25 +/- 0.09 and 3.03 +/- 0.50 Gy, respectively. There was a strong correlation between these two survival curve parameters (r = 0.98). Skin redness was found to linearly increase with time during radiotherapy. The slope of the increase differed markedly from patient to patient, with a range of a factor approx. 10. No correlation was found between SF2 and erythema response in the 24 evaluable patients (r = 0.13, p > 0.5). A similar lack of correlation was found using D10 as the radiosensitivity parameter (r = 0.12, p > 0.5). These data indicate that fibroblast radiosensitivity measured in vitro cannot be used to predict erythema reactions to radiotherapy in breast cancer patients.
从乳腺癌患者的打孔活检组织中获取成纤维细胞,在体外进行传代培养,并在早期传代时检测其放射敏感性。同时,采用反射分光光度法测量同一患者的皮肤红斑反应,以发红程度表示。在对胸壁进行为期4周的电子放疗前及放疗期间进行测量。在研究的59份活检组织中,对32份同时进行了放射敏感性和红斑反应研究。在24份样本中,获得了临床和实验室的可评估数据。在96孔板中进行群体生长测定,以磺酰罗丹明B的吸收作为细胞数量的染色剂,结果与集落形成测定结果吻合良好。使用人血清代替胎牛血清时,集落测定中的接种效率和生长速率更高。用人血清培养的细胞存活曲线大多呈指数形式,几乎没有肩区。将2 Gy时的存活参数(SF2)和产生10%存活所需的剂量(D10)用于与临床数据的相关性分析;这些参数分别为0.25±0.09和3.03±0.50 Gy。这两个存活曲线参数之间存在很强的相关性(r = 0.98)。发现放疗期间皮肤发红随时间呈线性增加。增加的斜率在患者之间差异显著,范围约为10倍。在24例可评估患者中,未发现SF2与红斑反应之间存在相关性(r = 0.13,p>;0.5)。以D10作为放射敏感性参数时,也发现了类似的无相关性结果(r =0.12,p>;0.5)。这些数据表明,体外测量的成纤维细胞放射敏感性不能用于预测乳腺癌患者放疗后的红斑反应。