Radiation Protective Effects Of GANRA-nanoparticles And Its Influence On Radio-sensitive MicroRNAs

Ionizing radiation widely exists in space,nuclear facilities and radiotherapy.It bring a great threat great to human life.Therefore,developing effective radiation protective drugs is of great significance.Many studies have found that GANRA drug play a good role for radiation protection,but GANRA drug is insoluble in water,that caused great difficulties for its research and application.At first,we packaged GANRA drug with hydrophilic nanoparticles material.The result showed that GANRA-nanoparticle had a better solubility than GANRA drug.The radiation protective effects of the GANRA-nanoparticles against X-rays irradiation in lymphoblast were studied in lymphoblast cells.Cytotoxicity and cell proliferation assay were conducted to evaluate the toxicity and radio-protective effects of GANRA-nanoparticles.The influence of these nanoparticles on the induction of genomic instability was determined using the cytokinesis-block micronucleus assay.Our results indicated that GANRA-nanoparticle exhibited low toxicity,while protecting lymphoblast from X-ray irradiation-induced damage.Moreover,GANRA nanoparticles acted as free radical scavengers.Secondly,previous research of our laboratory indicated that the expression of immunerelated micro RNAs?mi R-150,mi R-574,mi R-223 and mi R-34a?could be changed by ionizing irradiation in the circulating blood.Our study further investigated whether the expression of micro RNAs could be changed by ionizing irradiation in lymphoblast,by examining the expression of these micro RNAs in cells treated by different doses of X-rays irradiation.The results showed that mi R-150 and mi R-574 were up-regulated in lymphoblast treated with different doses of Xrays irradiation,while mi R-223 and mi R-34 a were down-regulated.Besides,these mi RNAs' relative expression levels could also be changed by GANRA-nanoparticle treatment.Then,we detected the expression of these micro RNAs in lymphoblast treated by different doses of X-rays or ¹2C⁶⁺ irradiation and GANRA-nanoparticle pretreatment.The results indicated that the expression changes of mi R-150,mi R-574,mi R-223 and mi R-34 a induced by X-ray or ¹2C⁶⁺ irradiation would be reduced by GANRA-nanoparticle pretreatment.Finally,we examined the role of mi R-574 in lymphoblast response to X-ray irradiation,by transfecting mi R-574 mimic.The results showed that overexpression mi R-574 led to a reduction not only in cellular activities but also in the micronucleus percentage and ROS in lymphoblast exposed to X-rays.In conclusion,GANRA-nanoparticle has the potential to be as a safe and efficient radioprotectant.The differences expression of the radiosensitive micro RNA induced by GANRAnanoparticle pretreatment in lymphoblast,may be a mechanism of GANRA-nanoparticle play the role of radiation protection.