Proton beam therapy is considered a step forward with respect to electromagnetic radiation, thanks to the reduction in the dose delivered. Among unwanted effects to healthy tissue, cardiovascular complications are a known long-term radiotherapy complication. The transcriptional response of cardiac tissue from xenografted BALB/c nude mice obtained at 3 and 10 days after proton irradiation covering both the tumor region and the underlying healthy tissue was analyzed as a function of dose and time. Three doses were used: 2 Gy, 6 Gy, and 9 Gy. The intermediate dose had caused the greatest impact at 3 days after irradiation: at 2 Gy, 219 genes were differently expressed, many of them represented by zinc finger proteins; at 6 Gy, there were 1109, with a predominance of genes involved in energy metabolism and responses to stimuli; and at 9 Gy, there were 105, mainly represented by zinc finger proteins and molecules involved in the regulation of cardiac function. After 10 days, no significant effects were detected, suggesting that cellular repair mechanisms had defused the potential alterations in gene expression. The nonlinear dose–response curve indicates a need to update the models built on photons to improve accuracy in health risk prediction. Our data also suggest a possible role for zinc finger protein genes as markers of proton therapy efficacy.
质子束疗法因能降低辐射剂量，被视为电磁辐射治疗领域的重要进展。在放疗对健康组织的不良影响中，心血管并发症是已知的长期放疗后遗症。本研究通过分析异种移植BALB/c裸鼠心脏组织在质子照射后3天和10天的转录组反应，探究剂量与时间对基因表达的影响，照射范围覆盖肿瘤区域及下方健康组织。实验采用三种剂量：2 Gy、6 Gy和9 Gy。中等剂量（6 Gy）在照射后3天产生最显著影响：2 Gy剂量下有219个基因表达发生改变，其中锌指蛋白类基因占比较高；6 Gy剂量下差异表达基因达1109个，以参与能量代谢和刺激反应的基因为主；9 Gy剂量下出现105个差异表达基因，主要表现为锌指蛋白及心脏功能调节相关分子。照射10天后未检测到显著效应，表明细胞修复机制可能消除了基因表达的潜在改变。这种非线性剂量-反应曲线提示，需要基于光子模型进行优化更新，以提高健康风险预测的准确性。我们的数据还表明，锌指蛋白基因可能作为质子疗法疗效的潜在生物标志物。
Impact on the Transcriptome of Proton Beam Irradiation Targeted at Healthy Cardiac Tissue of Mice
肿瘤(癌症)患者之家