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Ionizing radiation can directly produce ionizing particles or indirectly ionizing particles (or a mixture of both particles of ionizing radiation on the organism damage by radiation energy and direct role in the biological molecules, resulting in the damage of DNA, proteins, etc., leading to apoptosis, resulting in tissue and organ failure, such as hematopoietic tissue dysfunction, peripheral blood white blood cell count decreased, digestion, reduced function of the cardiovascular system, immune system disorders; ionizing radiation can also be indirect effects, through the water in the radiation important macromolecules produced in the reaction of free radicals, reactive oxygen species (ROS) attack nucleic acids, proteins, biofilm and cause the activation of transcription factors, leading to apoptosis, gene mutation, the occurrence of secondary tumors, such as leukemia, radiation-induced skin cancer and other ionizing radiation can be divided into radiation comprises charged particles (alpha particles, beta particles, protons, etc.) and uncharged particles (X-ray, gamma ray, neutron, etc.); and non-ionizing radiation, including light (visible light, infrared, ultraviolet ) and electromagnetic radiation (microwave, radio frequency, etc.) based on the radiation great harm to the body to study means of radiation injury prevention, looking for positive and effective drug prevention and treatment is of great significance. research radioprotectors mechanism includes two aspects, one of which promote DNA repair, inhibition of apoptosis, such as growth factors, protease inhibitors, etc., but its toxic side effects, reducing the clinical value; second is anti-oxidative stress, to reduce the generation of ROS such as sulfur-containing compounds, or phenols, etc., but the effect concentration high and low efficacy. Therefore, to find a non-toxic or low toxic, efficient radioprotectors is particularly important natural compound vanillin (3 - methoxy-4 - hydroxy - benzaldehyde), also known as vanillin, Hong Vanilla aldehyde, because of its antioxidant and anti-mutagenic activity are widely used in food additives. research reports the vanillin can clear X-ray and UV-induced ROS reduce chromosomal aberrations and cell micronucleus rate, enhanced DNA repair , but its role in high concentration, low activity this our group screened better radioprotective effects of vanillin derivatives cloves aldehydes (Syringaldehyde,, VND3207), pre-trials have demonstrated VND3207 more than vanillin clear free radicals, reduce radiation-induced DNA damage; VND3207 gamma ray induced normal cell genome damage and cell apoptosis in a good protective effect on the level of experimental animals, VND3207 can increase the number of white blood cells in the gamma-ray radiation, reducing rate of apoptosis of spleen cells after radiation and micronucleus formation rate. Based on the above theory and experiment, the subjects selected model of alpha particle radiation damage in cells, further to study VND3207 anti-radiation effect, and explore its mechanism from the cellular and molecular level (1) by immunofluorescence experiments established alpha particles damage the cell model results suggest that gamma-ray, alpha particle-induced gamma-H2AX clusters set point patchy damage area, fluorescence intensity, sustained long time, the ImageJ image statistical analysis of the corresponding conclusions; immunofluorescence results show that the alpha particle radiation intracellular p-CHK-2 and gamma-H2AX was common subcellular localization prompted to participate in P-Chk-2 alpha particle radiation repair of DNA damage response (2) vanillin derivative VND3207 normal cells detected by MTT assay results showed that by the 0-100μmol / L VND3207 treated cells, value-added and no significant change, at the same time compared with DMSO control group, the proliferation of no significant change, suggesting no significant toxicity to normal cells VND3207 0-100μmol / L (3) by cell colony formation assay showed that irradiation before or after irradiation to give a certain concentration the VND3207 drugs, can enhance cell alpha particle radiation damage resistance the same time, in different doses of irradiation, 50 micromol / L VND3207 can increase the radiation-sensitive cells resistant irradiation premedication effect better than the medication after irradiation reflected the issues previously reported VND3207 scavenging free radicals, thereby reducing the the indirect damage effects of radiation on DNA. Annexin Ⅴ labeling combined with flow cytometry 50μmol/LVND3207 exposed apoptosis occurred more good protective effect (4) DNA double-strand breaks ionizing radiation induced cell is the most serious form of injury. neutral single cell gel electrophoresis results showed that the VND3207 significantly reduced the rate of DNA double-strand breaks induced by 2.0Gyα particles, and was drug dependency; while 50 micromol / L VND3207 can effectively reduce the DNA in situ at different time points after 2.0Gyα particle radiation damage. micronucleus test, 20 micromol / L above the concentration VND3207 protection under radiation cell micronucleus rate decreased significantly; immune fluorescence and Western blot experiments are VND3207 effectively reduce the at 0.5Gyα particle nucleus gamma-H2AX expression (5) When DNA breaks injury, the body will start the DNA repair mechanism Western blot detection of alpha particle radiation intracellular repair protein, results showed that 5-100 micromol / L VND3207 can effectively improve the p-DNA-PKcs (S2056) the expression of alpha particle radiation, but no significant change in p-Chk-2 expression. immunofluorescence results show that can increase 50μmol/LVND3207 alpha particle radiation NF-B nuclear translocation, and resistance to radiation-induced apoptosis summary, VND3207 on normal cells without significant toxicity, and can effectively enhance the alpha particle cells after radiation of the radiation-sensitive resistance, improve the ability of cells to anti-apoptotic protection of radiation-induced DNA damage, and maintain the stability of the cell genome to increase the expression of repair proteins. Therefore, VND3207 is developed as the value of the anti-radiation drug and clinical radiation sickness provide a theoretical basis.
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