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宋 键
摘 要 我们采用分级采样及气相色谱/质谱分析方法，对柴油机排出颗粒物的分散度及其吸附的有机组分进行了测定，并用配套的短期测试系统结合相关癌基因表达等试验对其潜在致癌性及机制进行了探讨。 研究结果表明柴油车排出颗粒物以粒径≤3.3μm的颗粒为主，这部分粒径颗粒物的重量占总颗粒物的70%以上。对柴油车排出颗粒有机提取物的组分进行了分析检测。共检出111种化学物质，按粒径分析，随着粒径的减小，检出化学物质有增多的趋势，而且粒径小的颗粒所吸附的多环芳烃类物质和杂环化合物也较多。短期测试结果表明，柴油机排出颗粒物的遗传毒性在粒径≤1.1μm的部分表现的最强，随着颗粒粒径的增大，其毒性逐渐减小。结果与我们对颗粒物的化学成分分析所含的有机物（包括多环芳烃及杂环化合物）量一致。小鼠现场吸入试验结果表明柴油机排出物对小鼠染色体有一定的损伤作用，特别是小粒径颗粒物对染色体的损伤作用更强。在对柴油机排出颗粒物潜在致癌性的检测基础上，本研究通过用划痕染料示踪技术研究了它对细胞间隙连接通讯功能的影响；用流式细胞仪检测了DEPs对细胞的凋亡及细胞周期的改变；用免疫组织化学技术及点杂交技术对DEPs诱导转化的人胚肺细胞或经DEPs染毒动物的组织相关癌基因的表达进行了研究。结果表明DEPs提取物诱导细胞发生转化后，细胞的间隙功能有显著下降。细胞经DEPs染毒后，有影响细胞周期的作用，促进细胞由S期进入分裂期(M期)，即可以促进细胞的增殖。DEPs也表现出了对细胞凋亡有一定的抑制作用。 用免疫组织化学的方法检测柴油机排出颗粒物诱导发生转化后的人胚肺细胞相关癌基因ras、p53、p16、Bcl-2、c-myc的表达情况，发现p21、Bcl-2及c-myc蛋白表达阳性。DEPs染毒2、4、8周后小鼠肺组织的c-myc基因在RNA表达水平也明显增高。结果提示我们：DEPs一方面具有促进细胞分裂增殖的作用，另一方面对细胞的凋亡也有一定的抑制作用，另外它对细胞间隙连接通讯功能也有抑制作用，并可以促进一些相关癌基因的表达。这几方面的作用应是其导致细胞发生恶性转化、癌变的原因之一。 关键词：柴油机排出颗粒物 分散度 突变性 致癌性 癌基因表达 博士研究生期间发表的文章 1 . 宋健，叶舜华，祁萍萍.
不同粒径柴油机排出颗粒物的体外微核试验研究. 中国公共卫生 1997；13（3）：151－153
Song Jian (male) was born on Oct. 20 1964 at Jiangsu Province, P. R. China. Nationality: Chinese. At Sept. 1994 he became Ph.D. candidate in department of environmental health of Shanghai Medical University. Under the guidance of Prof. Ye Shun-hua and Hong Chuan-jie, he was awarded the Dr. degree of medicine at Shanghai Medical University on July 1997. Study on the Potential Carcinogenicity and it's Mechanism of Diesel Exhaust Particles with Various Diameters Abstract In order to study the size distribution of different diameter of diesel exhaust particles and the carcinogenicity of these particles, we used the fractionated sampling methods to detect the size distribution of particles and the GC/MS methods to analyze the organic component of diesel exhaust particles(DEPs). A series of short-term system tests and some related oncogene expression tests were used to detect the potential carcinogenicity and its mechanism of diesel exhaust particles. Based on all data presented in our studies, some conclusions are summarized as follows: 1. The majority of DEPs were less than 3.3um in diameter (the proportion by weight of this fraction was more than 70%), and this fraction of particles adsorbed more PAHs and other organic substances. 2. All the short-term tests demonstrated that in all kinds of various diameters particles those smaller particles showed stronger genotoxicity . 3. The mechanism of potential carcinogenicity of DEPs may include: (1)DEPs can inhibit the GJIC of cells, so the cells can grow free from the control of surrounding cells and be transformed easily. (2)DEPs can promote cells proliferation. DEPs also can inhibit the apoptosis of cells. 3) DEPs can promote some oncogene such as Bcl-2 gene, ras gene and c-myc gene expression. KEY WORDS: Diesel exhaust particles (DEPs) Size distribution Genotoxicity Carcinogenicity Oncogene expression
PUBLICATIONS AND THESIS 1. SONG Jian, YE Shun-hua, et al. The Inheritance Toxicity of Diesel Exhaust Particles. Foreign Medical Sciences, 1993, 20 (3):141 (in Chinese) 2. SONG Jian, YE Shun-hua, et al. Mutagenicity of Diesel Vehicle Exhaust Gas. Shanghai Environmental Sciences, 1994, 13(3): 23 (in Chinese) 3. SONG Jian, YE Shun-hua, et al. Mutagenicity of Diesel Exhaust Particles by Micronucleus Test in Mice. Modern Preventive Medicine , 1994,21:1 (in Chinese) 4. SONG Jian, YE Shun-hua, et al. Study on the Toxicity of Diesel Exhaust on Rat Pulmonary Cells. Journal of Health Toxicology, 1995, 9(3):153 (in Chinese) 5. SONG Jian, YE Shun-hua. Study on the Mutagenicity of Diesel Exhaust Particles. Biomedical and Environmental Sciences, 1995, 8:240 6. SONG Jian , YE Shun-hua, et al. Effect of Inhaling Diesel Exhaust on Micronucleus Frequency of Mice Bone Marrow Cells, Shanghai Environmental Sciences, 1996,15(2):35 (in Chinese) 7. SONG Jian, YE Shun-hua, et al. Transformation of Extracts of Diesel Exhaust Particles with Syrian Hamster Embryo Cells. Chinese Journal of Public Health, 1996, 15(1):28 (in Chinese) 8. SONG Jian, YE Shun-hua, et al. Potential carcinogenicity Research on Diesel Exhaust Particles. China Environmental Science, 1996,16(1):46(in Chinese) 9. SONG Jian, YE Shun-hua, et al. The Mutagenicity of Different Diameter of Diesel Particles by Unscheduled DNA Synthesis Test . Shanghai Environmental Sciences, 1996,15(9):34 (in Chinese) 10. SONG Jian, YE Shun-hua, et al. Study on Mutagenicity of Diesel Exhaust Particles in Different Diameter. Journal of Labour Medicine 1996；13(4)：209－212 11.SONG Jian, YE Shun-hua. Effects of diesel exhaust particle on gap junction intercellur communication. Journal of hygiene research 1997;26(3)145-147 12. SONG Jian, YE Shun-hua, et al. Studies on Gap Junction Intercellular Communication and p21, c-myc Protein Expression of the Cell Transformed by Diesel Exhaust Particles. Chinese Journal of Preventive Medicine (in press) | ||||||||