The Research Of The Bystander Effects Of The Neural Tumors Induced By The ⁷Li³⁺ Heavy Ion Irradiation

The bystander effect is a kind of radiation biological effect which has been widely accepted in recent years.Study on the bystander effect and its molecular mechanism and lay the theoretical foundation for radiation protection and wide application of nuclear physics,but also has an important guiding role and application in radiation protection,radiation risk assessment and clinical application of radiotherapy etc.The bystander effect of neural tumor cells induced by heavy ion irradiation is studied deeply to provide more perfect theoretical basis for the clinical cancer cure of the heavy ion radiotherapy,lay the theoretical foundation to make more scientific,efficient and reasonable protocol of heavy ion radiotherapy.This paper uses ⁷Li³⁺as the heavy ion source of radiation to establish the damage models of three kinds of the neural tumor cell lines including the neuroblastoma SH-SY5Y cells and two kinds of glioma cells including the U87 cell and the U251 cell.The biological effects of different dose induced by the bystander effects of heavy ion irradiation and Its underlying molecular mechanisms are researched deeply by the means of the medium transfer experiments.The results show that the bystander effects of heavy ion irradiation can induce the SH-SY5Y cells which are not irradiated to produce the inhibitive effect of proliferation.And in a certain dose range,the inhibitive effect of proliferation showed a certain time effect and dose effect.The bystander effects of heavy ion irradiation can also induced the glioma U87 cells to produce the inhibitive effect of proliferation,but there was no significant inhibitive effect of proliferation of the glioma U251 cells and It can stimulates the glioma U251 proliferation to a certain extent.In order to further investigate the causes of the changes in proliferation ability of nerve tumor cells induced by the bystander effects of the heavy ion irradiation,the mechanisms related to the changes in proliferation capacity of nerve tumor cells induced the bystander effects of heavy ion irradiation are researched from the cell cycle,apoptosis and Caspase activity in the paper.The experimental results show that the bystander effects of heavy ion irradiation can induce the changes of cell cycle,apoptosis and Caspase activity.In addition,the bystander effects of heavy ion irradiation can induce the neuroblastoma SH-SY5Y cells to produce the G1 phase arrest at low dose.While in the high dose,the G2 phase arrest is obvious.At the same time,in the middle and low dose,the bystander effects induce the significantly increase of apoptosis in the early stage,while in the high dose,the late apoptosis increased significantly.Moreover,the apoptosis and Caspase activity induced by the bystander effects increased more significantly in the low and middle dose than that in high dose.These results indicated that the changes of cell cycle and apoptosis induced by the bystander effects of heavy ion irradiation may be the important reasons that induce the inhibitory effects on proliferation of the neuroblastoma SH-SY5Y cells;the increased apoptosis induced by the bystander effects of heavy ion irradiation may be through the activation of the Caspase apoptosis pathway,the molecular mechanisms and the damage effects induced by the bystander effects of heavy ion irradiation may be different in the different dose.In this paper,the molecular mechanisms on the inhibition of proliferation of SH-SY5Y cells induced by the bystander effects of heavy ion irradiation are also researched from the aspects of the cell cycle,apoptosis and proliferation related signaling pathways.The results show that the inhibitive effect of proliferation of SH-SY5Y cells induced by the bystander effects of heavy ion irradiation is comprehensive effect of multiple factors and signaling pathways.The activation of the related signal pathways is not the same in different dose.This lays the foundation for the further research on the mechanisms and molecular mechanisms of the bystander effects induced by the irradiation,and provide a theoretical basis for the indirect damage effect of radiation biological effects on the long-term manned space engineering and clinical oncology in heavy ion radiotherapy.