Jones L A, Scott D, Cowan R, Roberts S A
Paterson Institute for Cancer Research, Christie CRC Research Centre, Manchester, UK.
Int J Radiat Biol. 1995 May;67(5):519-28. doi: 10.1080/09553009514550631.
There is a need for a simple, rapid assay for predicting normal tissue reactions in radiotherapy patients to reduce morbidity in sensitive patients and to allow dose escalation in resistant cases. Towards this goal we have investigated the gamma-ray sensitivity of lymphocytes from 16 breast cancer patients who had shown an exaggerated acute or late radiation reaction ('overreaction') of normal tissues after radiotherapy, using chromosome damage (dicentrics) as the endpoint because of its close relationship with cell killing. The use of a low dose-rate (LDR; 0.31 cGy min-1) was found to be better than a high dose-rate (170 cGy min-1) in discriminating between over-reactors and controls, as predicted (and here confirmed) from previous studies on ataxia-telangiectasia (A-T) homozygotes and heterozygotes. Five of seven patients with excessive early skin reactions (e.g. erythema, moist desquamation) showed abnormal radiosensitivity, manifested either as aberration yields above the control range after LDR exposure or as less sparing than controls. The average LDR yield for early over-reactions was significantly higher than for controls (p = 0.009) and average sparing was less (p = 0.0002). Two of 10 patients with late complications (fibrosis, telangiectasia) had LDR yields above the control range, but the average yield for late over-reactors was not significantly above that of controls. Unexpectedly, two patients (one early, one late reaction) had LDR aberration yields below the control range. Quantitatively our results are consistent with the notion that over-reacting breast cancer patients are carriers of the A-T gene. Pilot studies on controls showed that the sparing effect of LDR irradiation was increased by lowering the dose-rate to 0.13 cGy min-1 and by using micronuclei rather than metaphase damage as the endpoint. These modifications to the protocol will be used in a large-scale prospective study.
需要一种简单、快速的检测方法来预测放疗患者的正常组织反应，以降低敏感患者的发病率，并在抗性病例中实现剂量递增。为了实现这一目标，我们研究了16例乳腺癌患者淋巴细胞的γ射线敏感性，这些患者在放疗后正常组织出现了过度的急性或晚期放射反应（“过度反应”），由于染色体损伤（双着丝粒）与细胞杀伤密切相关，因此将其作为终点指标。正如之前对共济失调毛细血管扩张症（A-T）纯合子和杂合子的研究所预测（并在此得到证实）的那样，发现使用低剂量率（LDR；0.31 cGy min-1）在区分过度反应者和对照组方面比高剂量率（170 cGy min-1）更好。7例早期皮肤反应过度（如红斑、湿性脱皮）的患者中有5例表现出异常的放射敏感性，表现为LDR照射后畸变产率高于对照范围，或比对照组的放射保护作用小。早期过度反应的平均LDR产率显著高于对照组（p = 0.009），平均放射保护作用更小（p = 0.0002）。10例有晚期并发症（纤维化、毛细血管扩张）的患者中有2例LDR产率高于对照范围，但晚期过度反应者的平均产率并未显著高于对照组。出乎意料的是，有2例患者（1例早期反应，1例晚期反应）的LDR畸变产率低于对照范围。从定量角度来看，我们的结果与过度反应的乳腺癌患者是A-T基因携带者的观点一致。对对照组的初步研究表明，将剂量率降至0.13 cGy min-1并使用微核而非中期损伤作为终点指标，可以增强LDR照射后的放射保护作用。这些方案的修改将用于大规模前瞻性研究。
