Mechanisms Of Radiation-induced Effects Research Articles

Expression of DNA-PKcs and BRCA1 as prognostic indicators in nasopharyngeal carcinoma following intensity-modulated radiation therapy

The mechanisms of radiation-induced effects in cancer mainly involve double-strand breaks (DSBs) which are important in maintaining the stability of genes. The DNA repair genes breast cancer 1 (BRCA1) and DNA-dependent protein kinase catalytic subunit (DNA-PKcs) are capable of maintaining genetic stability through two distinct and complementary repair mechanisms for DNA DSBs, known as repair-homologous recombination (HR) and non-homologous end joining (NHEJ). DNA-PKcs is a member of the phosphatidylinositol 3-kinase (PI3K) family. The PI3K/AKT cell signaling pathway is implicated in cell migration and invasion. The BRCA1 protein is implicated in multiple complex cellular processes that are related to chromosome sensitivity to mutagens. To determine the protein expression and clinical implications of DNA-PKcs and BRCA1 in nasopharyngeal carcinoma (NPC) and cancer progression, we evaluated its expression status by immunohistochemistry in 87 patients who received intensity-modulated radiation therapy (IMRT). In NPC, negative expression of DNA-PKcs was detected in 35 of the 87 (40.2%) cancer types and was significantly associated with poor patient survival (P<0.05). The overexpression of DNA-PKcs and BRCA1 also led to significantly improved distant metastasis-free survival compared with patients who did not overexpress both genes, although the expression level of BRCA1 and distant metastasis-free survival were not closely correlated. In addition, multivariate analysis indicated that DNA-PKcs status is a predictive marker of distant metastasis-free survival. In conclusion, lower expression of DNA-PKcs may be correlated with higher distant metastasis in patients with NPC. DNA-PKcs may be a predictive marker of distant metastasis after IMRT, independent of the classical prognostic marker. BRCA1 may additionally exert a synergistic effect to predict distant metastasis-free survival.

DNA repair genes BRCA1 and DNA-PKcs have great potential in radiation therapy

Radiotherapy is a part of the front-line treatment regime for many cancers. The mechanisms of radiation-induced effects in cancers mainly involves double-strand breaks (DBS) which plays very important role in maintaining the stability of gene. As DNA repair gene breast cancer 1 (BRCA1) and DNA-dependent protein kinase catalytic subunit (DNA-PKcs) can act to maintain genetic stability though two distinct and complementary mechanisms for DNA DSB repair-homologous recombination (HR) and non-homologous end joining (NHEJ). Therefor, BRCA1 and DNA-PKcs are closely associated with radiation sensitivity, which means that they may be used as a useful tool to predict radio sensitivity in human tumour cells.

Sex-specific radiation-induced microRNAome responses in the hippocampus, cerebellum and frontal cortex in a mouse model

Ionizing radiation is an important treatment modality, but it is also a well-known genotoxic agent capable of damaging cells and tissues. Therefore radiation treatment can cause numerous side effects in exposed tissues and organs. Radiotherapy is a part of the front-line treatment regime for brain cancer patients, but can cause severe functional and morphological changes in exposed brain tissues. However, the mechanisms of radiation-induced effects in the brain are not well understood and are under-investigated. Recent data has implicated short RNAs, especially microRNAs, as important in radiation responses, yet nothing is known about radiation-induced changes in the brain microRNAome. We analyzed the effects of X-ray irradiation on microRNA expression in the hippocampus, frontal cortex, and cerebellum of male and female mice. Here, we report tissue-, time-, and sex-specific brain radiation responses, as well as show evidence of an interplay between microRNAs and their targets. Specifically, we show that changes in the expression of the miR-29 family may be linked, at least in part, to altered expression of de novo methyltransferase DNMT3a and changed global DNA methylation levels. Further, these sex-specific epigenetic changes may be correlated to the prevalence of radiation-induced cancers in males. We identified several microRNAs that can potentially serve as biomarkers of brain radiation exposure. In summary, our study may provide an important roadmap for further analysis of microRNA expression in different brain regions of male and female mice and for detailed dissection of radiation-induced brain responses.