Introduciton
Radiation, heavy metals, organic and particle pollutants widely exist in the environment, which may cause a potentially negative impact on the environment and human health. These environmental toxic and harmful pollutants can cause genetic damage in various forms and are one of the important factors resulting in various diseases. It has an important significance for health hazard early warning, prevention related diseases and establishment of health and safety standards through studying mechanisms of genetic damage induced by these environmental factors in cell, tissue and individual level. Research efforts in our laboratory focus on discovering the mechanism of interaction between organisms and environmental factors. Recently, we have published a series of papers in core journals of international medicine, environmental toxicology and radiation, and have good research work accumulation and reputation. All of these researchs are supported by the National Natural Science Fund, the National Science Foundation for Distinguished Young Scholars of China, One Hundred Person Project of the Chinese Academy of Sciences, National Program on Key Basic Research Project (973 Program), National High Technology Research and Development Program 863, and establish the good relationship with relevant laboratory of USA, Japan, British, France, et.al.
Research Direction
1, Genetic mechanism and clinical application of radiation
We focus on the biological regulation mechanism of radiation effects and the basic problems of the localization irradiation and radiation damage used in medical physics and radiation therapy, , utilizing various cellular and molecular biology methods to elucidate the roles of the cell signaling molecules involved in DNA damage repair, cell cycle regulation, and cell stress response et.al..
2, Interaction mechanism of biology and environmental factors
With a variety of models of biological systems, we study the biological responses of cell, tissue and individual exposured to environmental factors (such as nanoparticles, persistent toxic pollutants), and reveal the main biological response mechanism. Based on these research, we will develop characteristic biomarkers which will provide important reference basis for health hazard warning and establishing protective measures.
3, Application of bio-nanomaterials in the environment and human health
Combination of nanomaterials and biological modification technology, we focus on developing new methods to realize the rapid detection harmful substances or pathogenic microorganism in the environment and food. We also do some research to enhance the compatibility of nanomaterials, and increase the availability and targeting of drugs in vivo.
4, Radiation in medical physics
Radiotherapy is one of the main methods in the treatment of malignant tumors. Radiosurgery treatment planning system provides a working platform and quality assurance for treatment scheme and implementation of radiotherapy, so as to achieve the maximum of killing tumor cells and to effectively protect the surrounding organs and other normal tissues, in which the key is how to improve the accuracy and ensure the curative effect in treatment. Based on the interdisciplinary talent advantage and laboratory studies, the radiation medical physics group of FDS team, are carrying out interdisciplinary, application and industrialization research of the key physical technique for realizing precise radiotherapy.
5, High-throughput screening and directed evolution of protein
Directed evolution of biological macromolecules can obtain the high performance enzyme and antibody which needed in the industry and pharmaceutical industry in a relative short time. It becomes a research hotspot to obtain high activity of biological products in modern food industry and pharmaceutical research by mutagenesis, surface display in combination with high-throughput screening technology. The research of evolution of enzyme and improvement of antibody and antigen performance meets the needs of social and economic development.
Research Progress
1. Bystander effects of early process and the damage signaling generation and transmission.
Radiation-induced bystander effect is the focus of international radiation biology research, and studying its mechanism has important significance for cancer radiation therapy and establishing radiation protection models. Currently, the biological effects of radiation bystander effects, such as survival, mutation, gene expression, or carcinogenesis, mostly reflect the situation after a few hours or longer. But it is not clear for start-up and early process of radiation bystander effects. We established DNA double strand breaks (DSBs) technical methods to assess early process of radiation bystander effects (《Radiation Research》, 2005), and investigated the relationship between radiation damage signaling transduction and the intensity of radiation damage（《Carcinogenesis》, 2006）. We found that constitutive nitric oxide produced by radiation cells may be the key signaling molecule which induced the DSBs in the unirradiated bystander cells (《Oncogene》, 2007), and we also studied the role of mitochondria and cytochrome c in these processes (《British Journal of Cancer》, 2009). Meanwhile, we also further explore the effects of environmental factor such as high NaCl for response of radiation bystander effects and damage signaling（《Mutation Research》, 2007, 2008, 2009）. These researches received widespread attention at home and abroad. Our research about the relationship between mitochondria and radiation bystander effects has highlighted by 《Nature China》titled by “Cancer Therapy: Effects of Radiation”, which considered our results has important significance for exploring the toxicological effects of radiation therapy.
Radiation bystander effects have been found in many type of cells. Previous studies showed that the role of radiation damage by the irradiation range is greater than the physical target range, but it is not known whether this damage is limited to a specific tissue, organs or the entire irradiated individuals. Using the Arabidopsis embryo as research object, we quantitatively irradiated the shoot apical meristem of Arabidopsis by single-particle microbeam to study the effects of non-irradiated tissue induced by irradiated the stem end of the meristem tissue. Our results showed the presence of radiation levels at the plant individual long-term side effects, and demonstrated that free radicals and growth hormone-dependent gene expression plays an important role in this process《Radiation Research》 (2007).
2. The mechanism of genetic damage induced by environmental hazardous factors
Diesel particulate extract (DPE) is an important environmental pollutants, but its mechanism of interaction with other factors is not clear. We studied the genetic toxicity of DPE from cell level《Toxicology》 (2007), and found that UVA could increase the mutation rate of low dose DPE and demonstrated that the singlet oxygen plays an important role in this process (《Environmental Health Perspectives》, 2009).
Nano-scale materials generally exist in nature. However, with the development of nanotechnology and expand production of nanomaterials, the potential toxicity of nanomaterials to the environment and human health has been widely concerned by the scientific community and government departments. Using transgenic mouse mutation system, we found that the nano-TiO2 and C60 have genetic toxicity and ONOO free radicals play an important role in this effect. And the nano-TiO2 can induce cell apoptosis in C.elegans, and the apoptosis rate increased with the dosage increased. Related results and papers have been published on “Particle and Fibre Toxicology” (2009). Studying in the living levels is an important foundation to reveal the mechanism of the interaction between environmental factors and organisms. Using the model of C.elegans, we studied the genetic toxicity of arsenic and found that exposed to arsenic in low dose not only affected brood size but also leaded to reproductive gland cell cycle arrest and apoptosis（《Chemical Research in Toxicology》，2007）. We further studied the apoptosis signaling pathway induced by exposure to low level of cadmium and arsenic, and found that apoptosis of germ cells induced by cadmium and arsenic does not depend on the DNA damage response genes, HUS1 and p53, but depends on ASK1/2-MKK7-JNK and ASK1/2-MKK3/6-p38 signaling pathway (《Chemical Research in Toxicology》, 2008；《Toxicological Sciences》, 2007). Our results have been highlighted by《Chemical Research in Toxicology》with the title “Arsenite-Induced Apoptosis”.
3. The mechanism of low energy ion effects
As a new subject, researches of biological effect on low energy ion beams have made some achievements. Recent studies have shown that high-energy particle radiation injury in fact is the combined result of particle tracks on a series of low-energy particle radiation events. However, with the limitation of the low tolerance of mammalian cells to high vacuum environment, it has been failed to implant ion to mammalian cells. We established an experimental method of cell survival in a vacuum condition based on analysis of the cell survival under vacuum conditions《Cryobiology》（2004）. On this basis, we studied the level and characteristic of mammalian cell gene mutation induced by nitrogen ion beam (5-20 kev). Our results show that 20kev N+ ion beam can make the rate of CD59 gene mutation increase 2-3 times, and the mutation rate was not associated with ion beam energy《Nuclear Instruments and Methods in Physics Research B》 （2005）.
At the individual level, through the shielding irradiation on Arabidopsis apical meristem, we found that non-irradiation shoot apical meristem (SAM) and root apical meristem (RAM) had a significant change in development. This result showed that the damaged induced by radiation can be transduced to SAM and RAM which caused developmental changes. This demonstrated that long range transduction radiation injury may be one of the main mechanisms of low energy heavy ion irradiation effect《Radiation Research》 （2008）. “This paper reports the novel in vivo bystander effect of light-energy heavy ions in Arabidopsis seeds. The data presented are intriguing and important” which is commented in《Radiation Research》. 4. Radiation in medical physics
Based on depth research of precise radiotherapy and achieved a series of results, FDS team has successful developed a précis radiotherapy planning system (ARTS) with independent intellectual property rights（《Chinese Physics C》，2008）, MLC and IMRT dose verification software（《Phys. Med. Biol》, 2006）. The innovative study contents include: the calculation method of modeling, rapid and high precision coupling method and reverse hybrid muti-objective optimization method.
Achievements
1. Guo X., Bian P., Liang J., Wang Y., Li L., Wang J., Yuan H., Chen S., Xu A., and Wu L., Synergistic effects induced by a low dose of diesel particulate extract and ultraviolet-A in Caenorhabditis elegans: DNA damage-triggered germ cell apoptosis. Chem Res Toxicol, 2014. 27(6): p. 990-1001.
2. Guo X., Sun J., Bian P., Chen L., Zhan F., Wang J., Xu A., Wang Y., Hei T.K., and Wu L., Radiation-induced bystander signaling from somatic cells to germ cells in Caenorhabditis elegans. Radiat Res, 2013. 180(3): p. 268-75.
3. Wang X.F., Zhao G.P., Liang J.T., Jiang J., Chen N., Yu J., Wang Q.S., Xu A., Chen S.P., and Wu L.J., PFOS-induced apoptosis through mitochondrion-dependent pathway in human-hamster hybrid cells. Mutation Research-Genetic Toxicology and Environmental Mutagenesis, 2013. 754(1-2): p. 51-57.
4. Chen S., Qiu J., Chen C., Liu C., Liu Y., An L., Jia J., Tang J., Wu L., and Hang H., Affinity maturation of anti-TNF-alpha scFv with somatic hypermutation in non-B cells. Protein Cell, 2012. 3(6): p. 460-9.
5. Xu S.M., Yuan H., Chen S.P., Xu A., Wang J., and Wu L.J., Selection of DNA aptamers against polychlorinated biphenyls as potential biorecognition elements for environmental analysis. Analytical Biochemistry, 2012. 423(2): p. 195-201.
6. Xu S.M., Yuan H., Xu A., Wang J., and Wu L.J., Rapid Synthesis of Stable and Functional Conjugates of DNA/Gold Nanoparticles Mediated by Tween 80. Langmuir, 2011. 27(22): p. 13629-13634.
7. Zhao G., Wang J., Wang X., Chen S., Zhao Y., Gu F., Xu A., and Wu L., Mutagenicity of PFOA in mammalian cells: role of mitochondria-dependent reactive oxygen species. Environ Sci Technol, 2011. 45(4): p. 1638-44.
8. Han W., Wu L., Chen S., and Yu K.N., Exogenous carbon monoxide protects the bystander Chinese hamster ovary cells in mixed coculture system after alpha-particle irradiation. Carcinogenesis, 2010. 31(2): p. 275-80.
9. Bao L.Z., Xu A., Tong L.P., Chen S.P., Zhu L.Y., Zhao Y., Zhao G.P., Jiang E.K., Wang J., and Wu L.J., Activated Toxicity of Diesel Particulate Extract by Ultraviolet A Radiation in Mammalian Cells: Role of Singlet Oxygen. Environmental Health Perspectives, 2009. 117(3): p. 436-441.
10. Chen S.P., Zhao Y., Zhao G.P., Han W., Bao L.Z., Yu K.N., and Wu L.J., Up-regulation of ROS by mitochondria-dependent bystander signaling contributes to genotoxicity of bystander effects. Mutation Research-Fundamental and Molecular Mechanisms of Mutagenesis, 2009. 666(1-2): p. 68-73.
11. Pei B., Wang S.C., Guo X.Y., Wang J., Yang G., Hang H.Y., and Wu L.J., Arsenite-induced germline apoptosis through a MAPK-dependent, p53-independent pathway in Caenorhabditis elegans. Chemical Research in Toxicology, 2008. 21(8): p. 1530-1535.
12. Wang S.C., Tang M.L., Pei B., Xiao X., Wang J., Hang H.Y., and Wu L.J., Cadmium-induced germline apoptosis in Caenorhabditis elegans: The roles of HUS1, p53, and MAPK signaling pathways. Toxicological Sciences, 2008. 102(2): p. 345-351.
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