Kuwashima Y, Majima H, Okada S
Department of Radiation Biophysics, Faculty of Medicine, University of Tokyo, Japan.
Int J Radiat Biol. 1988 Jul;54(1):91-104. doi: 10.1080/09553008814551531.
Human melanoma, HMV-I, multicellular spheroids were irradiated and cure was determined by the absence of cellular outgrowth. Their cellular radiosensitivity was measured by the colony-forming ability of cells dispersed from the spheroid. Analysis of radiocurability of spheroids in terms of their cellular radiosensitivity predicted three necessary conditions: a linearity of dose versus the double-minus logarithm of curability; constancy of a critical cell number; and constancy of cellular radiosensitivity. These conditions were found to exist in the observed data for each of three size classes of spheroids. Analysis suggests that cellular radiosensitivity in multicellular spheroids with diameters of 250 and 400 microns was different from that of monolayers, and that the increase of spheroid-control doses was found to be a function of cellular radiosensitivity, total cell number per spheroid and a critical cell number. The critical cell number increased from 0.8 in a 150 microns spheroid to 4 in a 250 microns spheroid and to 57 in 400 microns spheroid. This number is a unique characteristic of multicellular systems and is one important factor in determining their radiocurability. X-ray-induced growth delay of spheroid size was increased with increasing dose. At high doses a sharp increase in delay time was seen, sometimes accompanying fragmentation of spheroids at late postirradiation times. The clonogenic activity of these fragments may serve as a model of exfoliation, the first step of radiation-induced metastasis.
对人黑色素瘤HMV-I多细胞球体进行照射，并通过细胞生长的缺失来确定治愈情况。通过从球体分散的细胞的集落形成能力来测量其细胞放射敏感性。根据细胞放射敏感性分析球体的放射可治愈性预测了三个必要条件：剂量与治愈性的双负对数之间的线性关系；临界细胞数的恒定；以及细胞放射敏感性的恒定。在观察到的三种大小类别的球体数据中都发现了这些条件。分析表明，直径为250和400微米的多细胞球体中的细胞放射敏感性与单层细胞不同，并且发现球体对照剂量的增加是细胞放射敏感性、每个球体的总细胞数和临界细胞数的函数。临界细胞数从150微米球体中的0.8增加到250微米球体中的4，再增加到400微米球体中的57。这个数字是多细胞系统的一个独特特征，是决定其放射可治愈性的一个重要因素。X射线诱导的球体大小生长延迟随着剂量增加而增加。在高剂量时，延迟时间急剧增加，有时在照射后期伴有球体破碎。这些碎片的克隆活性可作为脱落的模型，即辐射诱导转移的第一步。
