Hermens A F, Bentvelzen P A
Institute of Applied Radiobiology and Immunology, ITRI-TNO, Rijswijk, The Netherlands.
Cancer Res. 1992 Jun 1;52(11):3073-82.
Rat R2k rhabdomyosarcoma cells were transfected with the human H-ras oncogene, which resulted in increased resistance to cell kill in vitro by a single dose of 137Cs gamma-rays. A subline carrying one oncogene showed an increase in the quasi-threshold dose (Dq) from 0.88 to 1.48 Gy. Another subline containing six oncogenes not only had an increased Dq of 1.59 Gy but also showed an increase in the dose reducing cell survival to a fraction of e-1 = 0.37 (D0) from 1.25 to 1.76 Gy. Analysis of the cell survival data according to the linear-quadratic formalism indicated that a decrease in the value of the coefficient of the linear component alpha is associated with a H-ras-mediated increase in radioresistance. In fractionated irradiation experiments it was observed that with a dose of 1 Gy/fraction a 1.8 times higher dose for an isoeffect of 10% cell survival (D10) was needed for a subline with one H-ras oncogene, while with fraction doses of 2 or 4 Gy only a 1.2 times higher D10 was found. This indicates a more efficient repair of radiation-induced damage in the transfected subline. Tumors arising in the rat gastrocnemius muscle inoculated with cultured cells were irradiated with different doses of 300-kV X-rays. A single dose of 45 Gy was found to result in a 6% cure rate for the subline containing one H-ras oncogene and a 32% for the parental line. When a priming dose of 45 Gy was followed by fractionated irradiation with 1 Gy/fraction, an extra dose of 51 Gy would be needed to obtain a 75% cure rate for the transfected subline. An extra dose of only 10 Gy would be needed for the parental line. The percentage cure per unit of dose for the parental line irradiated with 1 Gy/fraction was estimated to be 4.3%.Gy-1, whereas for the transfected tumor line it was 1.4%.Gy-1. This means that a 3.0 times higher cumulated absorbed dose would be needed for enhancing the cure rate from 32% to 75% in the subline with H-ras than for the parental line. With 2 Gy/fraction the difference in extra doses required for obtaining isolevels of cure rates was found to be small, a factor of 1.4. The results indicate that in the course of fractionated irradiation with 1 Gy/fraction, in vivo repair is much more efficient in the transfected subline.
将人H-ras癌基因转染大鼠R2k横纹肌肉瘤细胞，结果使其对单剂量137Csγ射线体外杀伤的抗性增强。携带一个癌基因的亚系准阈剂量（Dq）从0.88 Gy增加到1.48 Gy。另一个含有六个癌基因的亚系不仅Dq增加到1.59 Gy，而且将细胞存活分数降低至e-1 = 0.37（D0）的剂量也从1.25 Gy增加到1.76 Gy。根据线性二次模型分析细胞存活数据表明，线性成分α系数值的降低与H-ras介导的放射抗性增加相关。在分次照射实验中观察到，对于携带一个H-ras癌基因的亚系，当剂量分割为1 Gy/次时，要达到10%细胞存活等效效应（D10）所需剂量高出1.8倍，而当分割剂量为2或4 Gy时，D10仅高出1.2倍。这表明转染亚系中辐射诱导损伤的修复更有效。用培养细胞接种大鼠腓肠肌产生的肿瘤用不同剂量的300 kV X射线照射。发现单剂量45 Gy时，携带一个H-ras癌基因的亚系治愈率为6%，亲代系为32%。当45 Gy的起始剂量后接着以1 Gy/次进行分次照射时，转染亚系要达到75%的治愈率需要额外51 Gy的剂量。亲代系仅需要额外10 Gy的剂量。亲代系以1 Gy/次照射时每单位剂量的治愈率估计为4.3%·Gy-1，而转染肿瘤系为1.4%·Gy-1。这意味着在携带H-ras的亚系中，将治愈率从32%提高到75%所需的累积吸收剂量比亲代系高3.0倍。当分割剂量为2 Gy/次时，达到相同治愈率所需额外剂量的差异较小，为1.4倍。结果表明，在以1 Gy/次进行分次照射过程中，转染亚系在体内的修复效率更高。
