RESUMO
Individual radiosensitivity is a critical problem in radiotherapy because of the treatment restrictions it imposes. We have tested whether induction/repair of genomic lesions correlates with the acute cutaneous effects of radiotherapy. Peripheral blood samples of 56 healthy volunteers and 18 patients with breast cancer were studied. DNA damage and DNA repair capacity were assessed in vitro (alkaline comet assay). Patients without skin reaction did not show significant differences from healthy individuals, with respect to either initial or radiation-induced DNA damage. Similar DNA repair kinetics, fitting a decreasing exponential response, were observed in both groups, and there were no significant differences in residual genotoxic damage. In contrast, patients exhibiting acute side effects showed significantly lower DNA repair ability and significantly more residual damage, compared to patients without radiotoxicity. This approach may help to identify patients who are at greater risk of radiotherapy side effects. However, many other factors, such as dosimetry, irradiated volume, and lifestyle should also be considered in the evaluation of individual radiosensitivity.
Assuntos
Reparo do DNA/efeitos da radiação , Tolerância a Radiação/genética , Adulto , Neoplasias da Mama/genética , Neoplasias da Mama/radioterapia , Ensaio Cometa/métodos , Dano ao DNA/genética , Dano ao DNA/efeitos da radiação , Relação Dose-Resposta à Radiação , Feminino , Humanos , Linfócitos/efeitos da radiação , Lesões por Radiação/genética , Pele/efeitos da radiação , Adulto JovemRESUMO
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⯵M 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⯵M exerted a genotoxic effect and that this concentration also had the capacity of modulating the cytomolecular damage induced by 4 and 16â¯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⯵M dose of RSV observed in the tumor system, they also showed a radio-protective effect at the lowest dose (15⯵M). 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.
Assuntos
Antineoplásicos Fitogênicos/farmacologia , Proliferação de Células , Raios gama , Neoplasias Pulmonares/patologia , Linfócitos/patologia , Radiossensibilizantes/farmacologia , Resveratrol/farmacologia , Adulto , Animais , Células CHO , Células Cultivadas , Cricetinae , Cricetulus , Feminino , Voluntários Saudáveis , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/radioterapia , Linfócitos/efeitos dos fármacos , Linfócitos/efeitos da radiação , Adulto JovemRESUMO
Sweet orange (Citrus sinensis), one of the most important fruit crops worldwide, may suffer from disease symptoms induced by virus infections, thus resulting in dramatic economic losses. Here, we show that the infection of sweet orange plants with two isolates of Citrus psorosis virus (CPsV) expressing different symptomatology alters the accumulation of a set of endogenous microRNAs (miRNAs). Within these miRNAs, miR156, miR167 and miR171 were the most down-regulated, with almost a three-fold reduction in infected samples. This down-regulation led to a concomitant up-regulation of some of their targets, such as Squamosa promoter-binding protein-like 9 and 13, as well as Scarecrow-like 6. The processing of miRNA precursors, pre-miR156 and pre-miR171, in sweet orange seems to be affected by the virus. For instance, virus infection increases the level of unprocessed precursors, which is accompanied by a concomitant decrease in mature species accumulation. miR156a primary transcript accumulation remained unaltered, thus strongly suggesting a processing deregulation for this transcript. The co-immunoprecipitation of viral 24K protein with pre-miR156a or pre-miR171a suggests that the alteration in the processing of these precursors might be caused by a direct or indirect interaction with this particular viral protein. This result is also consistent with the nuclear localization of both miRNA precursors and the CPsV 24K protein. This study contributes to the understanding of the manner in which a virus can alter host regulatory mechanisms, particularly miRNA biogenesis and target expression.