Radiotherapy is widely used for cancer treatment. However, its adverse effects that may develop during the course of treatment have forced to search agents to protect biological systems against the deleterious effects of radiation. Resveratrol (3,4,5-trihydroxy-trans-stilbene; RSV) is a natural polyphenol currently promoted for its beneficial pleiotropic effects on health, which has been shown to exhibit antioxidant properties while inhibiting the growth of tumor cells. In radioresistant tumors, RSV could contribute to reduce recurrence and treatment failure. We evaluated the radiomodulatory and genotoxic effects of RSV in CHO-k1 and A549 cell lines and in peripheral human blood lymphocytes through both conventional and hypofractionated protocols, due to the widespread use of hypofractionation in recent years. RSV genotoxic and cytotoxic action was assessed at 15 and 60 μM concentrations with the comet and the MTT assay and in cell proliferation experiments. Our results show that RSV administration to tumor cells at a dose of 60 μM exerted a genotoxic effect and that this concentration also had the capacity of modulating the cytomolecular damage induced by 4 and 16 Gy. These doses are delivered in conventional and hypofractionated radiotherapy, respectively. In both treatments, a radiosensitizing effect was evidenced by the decrease in cell viability that was exacerbated over time. These effects were not found in peripheral blood, suggesting that RSV had a dual response. Although the results obtained in CHO-k1 transformed cells corroborated the genotoxic effect of the 60 μM dose of RSV observed in the tumor system, they also showed a radio-protective effect at the lowest dose (15 μM). While more studies are necessary, our results together with the good systemic tolerance of RSV and the lack of toxicity position the compound as a potential candidate for the prevention and treatment of cancer as well as for the optimization of the radiotherapeutic ratio.

中文翻译：

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评估白藜芦醇的放射治疗潜力。

放射疗法被广泛用于癌症治疗。然而，其在治疗过程中可能产生的不利影响已迫使寻找试剂以保护生物系统免受辐射的有害影响。白藜芦醇（3,4,5-三羟基-反式-二苯乙烯； RSV）是一种天然多酚，目前因其对健康的有益多效作用而得到推广，已显示出抗氧化特性，同时抑制肿瘤细胞的生长。在放射线敏感性肿瘤中，RSV可能有助于减少复发和治疗失败。由于近年来低分割的广泛使用，我们通过常规和低分割的方案评估了RSV在CHO-k1和A549细胞系以及外周血淋巴细胞中的辐射调节和遗传毒性作用。通过彗星和MTT分析以及细胞增殖实验，以15和60μM的浓度评估了RSV的遗传毒性和细胞毒性作用。我们的结果表明，以60μM的剂量对肿瘤细胞进行RSV施用具有遗传毒性作用，并且该浓度还具有调节4 Gy和16 Gy诱导的细胞分子损伤的能力。这些剂量分别在常规和次分割放疗中递送。在两种治疗中，随着时间的推移，细胞活力的下降都加剧了放射增敏作用。在外周血中未发现这些作用，表明RSV具有双重反应。尽管在CHO-k1转化细胞中获得的结果证实了在肿瘤系统中观察到的60μM剂量RSV的遗传毒性作用，他们还显示了最低剂量（15μM）的辐射防护作用。尽管还需要进行更多研究，但我们的结果以及对RSV的良好系统耐受性和缺乏毒性，使得该化合物成为预防和治疗癌症以及优化放射治疗比例的潜在候选者。