Wazer D E, Joyce M, Jung L, Band V
Department of Radiation Oncology, Tufts University School of Medicine, New England Medical Center, Boston, MA 02111.
Int J Radiat Oncol Biol Phys. 1993 Apr 30;26(1):81-8. doi: 10.1016/0360-3016(93)90176-v.
To investigate growth regulation and radiosensitivity in surviving clonogens after fractionated irradiation.
Four breast carcinoma cell lines isolated from the primary tumor (21NT, 21PT) and metastases (21MT-1, 21MT-2) of a single patient were exposed to cumulative radiation doses of 30 Gy yielding cell lines designated-IR with respect to their parent. The irradiated lines were then compared to their parent for serum-and growth factor-requirements under defined media conditions, ability to proliferate in soft agar, concentration of TGF-alpha in conditioned medium, and radiosensitivity.
The irradiated lines showed no change in proliferative doubling times under serum- and growth factor-supplemented media conditions. A single line, 21MT-1-IR, acquired a limited ability to proliferate in serum-and growth factor-deplete medium with a day 2-4 doubling time of 44.5 hr. Three lines, 21MT-1-IR, 21MT-2-IR, and 21NT-IR, formed colonies in soft agar in contrast to none of the unirradiated parent lines. There were significant 6-8 fold increases in conditioned media TGF-alpha concentrations for 21MT-2-IR and 21NT-IR cells. The 21MT-1-IR and 21NT-IR cells were significantly less radiosensitive than their respective parent lines. This decrease in radiosensitivity appeared to be at least partially mediated by a released factor as the radiosensitivity of 21MT-1 cells was significantly decreased by pre-incubation with conditioned medium from 21MT-1-IR cells.
Radiation-induced changes in growth phenotype vary with respect to clonal origin of the cell line and may influence the radiosensitivity of surviving clonogens after fractionated treatment.
研究分次照射后存活克隆原细胞的生长调控和放射敏感性。
从一名患者的原发性肿瘤（21NT、21PT）和转移灶（21MT - 1、21MT - 2）中分离出的四种乳腺癌细胞系，接受30 Gy的累积辐射剂量，相对于其亲代细胞系产生了命名为 - IR的细胞系。然后在特定培养基条件下，将照射后的细胞系与其亲代细胞系比较血清和生长因子需求、在软琼脂中增殖的能力、条件培养基中TGF - α的浓度以及放射敏感性。
在补充血清和生长因子的培养基条件下，照射后的细胞系增殖倍增时间没有变化。单一细胞系21MT - 1 - IR在血清和生长因子缺乏的培养基中获得了有限的增殖能力，第2 - 4天的倍增时间为44.5小时。与未照射的亲代细胞系均未形成菌落不同，21MT - 1 - IR、21MT - 2 - IR和21NT - IR这三个细胞系在软琼脂中形成了菌落。21MT - 2 - IR和21NT - IR细胞的条件培养基中TGF - α浓度显著增加了6 - 8倍。21MT - 1 - IR和21NT - IR细胞的放射敏感性明显低于其各自的亲代细胞系。这种放射敏感性的降低似乎至少部分是由一种释放因子介导的，因为用21MT - 1 - IR细胞的条件培养基预孵育后，21MT - 1细胞的放射敏感性显著降低。
辐射诱导的生长表型变化因细胞系的克隆起源而异，可能影响分次治疗后存活克隆原细胞的放射敏感性。
