Purpose: Radiotherapy is an effective tool for cancer control, but side effects on normal tissue limit its therapeutic effectiveness. Thus, the search for agents that may allow the use of high doses of radiation but exerting a differential protection to healthy tissue is of current concern. Resveratrol (3, 5, 4'-trihydroxy-trans-stilbene) (RSV) is a polyphenol with pleiotropic benefits for health due to its antioxidant and anti-inflammatory properties. Recent findings suggest that RSV could be promising in the fight against cancer since it inhibits the growth of tumor cells and optimizes radiotherapy. However, evidence in rodents and human beings is inconsistent. The aim of this study was to evaluate the radiomodulatory capacity of RSV on human lymphocytes.
Materials and methods:To study these properties of RSV, human peripheral blood lymphocytes from 20 healthy women undergoing in vivo RSV treatment with 50 mg/day doses were irradiated. The genotoxic damage was assessed by the comet assay, also called single cell gel electrophoresis (it makes it possible to measure the extent of the DNA migration from individual cells, detecting the genomic damage present in each cell).Results: No differences were observed in basal clastogenic damage among samples without irradiation. There was only a slight radiation-induced clastogenic damage. The Damage Index (DI) value had a statistically significant increase in the exposed groups in comparison with the control groups (p<0.0001), but a statistically significant decrease of the DI value was observed in samples irradiated after treatment with RSV compared to pre-treatment samples (p<0.0001).
Conclusion:The RSV used as a dietary supplement had radioprotective properties, without exerting cytotoxic effect. The potential utility of RSV to optimize the radiotherapeutic ratio in cancer treatments using radiotherapy should be considered.
The extreme demand on health systems due to the COVID-19 pandemic has led to reconsider hypofractionation. Although the best clinical effi cacy of these schemes is being demonstrated, the biological bases have not been established. Thus, after validating basic clinical parameters, through complementary in vitro models, we characterized the cellular and molecular mechanisms of hypofractionation protocols.Cell cultures of human lung cancer cell line A549 were irradiated with 0, 2, 4, 8, 12, 16 and 20 Gy. The clastogenic, cytotoxic, proliferative and clonogenic capacities and bystander effect were evaluated. In addition, we assessed survival and toxicity in a retrospective study of 49 patients with lung cancer. Our fi ndings showed that the greater effi cacy of ablative regimens should not only be attributed to events of direct cell death induced by genotoxic damage, but also to a lower cell repopulation and the indirect action of clastogenic factors secreted. These treatments were optimal in terms of 1-and 2-year overall survival (74 and 65%, respectively), and progression-free survival at 1 and 2 years (71 and 61%, respectively). The greater effi cacy of high doses per fraction could be attributed to a multifactorial mechanism that goes beyond the 4Rs of conventional radiotherapy.
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