THAI NGUYEN UNIVERSITY UNIVERSITY OF AGRICULTURE AND FORESTRY NATIONAL TSING HUA UNIVERSITY THAVISACK MIVONGSACK TITLE: POTENTIAL GENE-NETWORK FOR THE HEALTH EFFECT OF EXPOSURE TO PCB/FS ON HUMAN DIFFUSE LARGE CELL LYMPHOMA BACHELOR THESIS Study Mode:Full-time Major: Environmental science and management Faculty:International Programs Office Batch: 2013-2017 Thai Nguyen, 21/12/2017 n DOCUMENTATION PAGE WITH ABSTRACT Thai Nguyen University of Agriculture and Forestry Degree Program Bachelor of Environmental Science and Management Student name THAVISACK MIVONGSACK Student ID DNT 1253110103 Thesis Title Potential gene-network for the health effect of exposure to pcb/fs on human diffuse large cell lymphoma Supervisor (s) Prof. Chun-Yu Chuang, Associate. DRTran Van Dien Abstract: The thesis describes the Lymphoma is the most top cancers in the worldwide, and the incidence rises strikingly since the last half of 20thcentury. Lymphoma is a cancer affecting the immune system; the major risk factor is associated with exposure to occupational or environmental chemicals.
Polychlorinated biphenyls (PCBS) are a class of organic chemicals, known as congeners that have been used in a variety of commercial products. PCBs were used in caulking, electronics, fluorescent light ballasts and other building materials from the 1950s to the late 1970s. Buildings built or renovated during that time may contain PCBs in caulking and other materials. PCBare very stable mixtures that are resistant to extreme temperature and pressure.
PCBS were used widely in electrical equipment like capacitors and transformers. They also were used in hydraulic fluids, heat transfer fluids, lubricants, and plasticizers. i n PCBs have been released into the environment through spills, leaks from electrical and other equipment, and improper disposal and storage. It is estimated that more than half of the PCBS produced have been released into the environment.
Once in the environment, PCBS can be transported long distances and they bind strongly to soil and sediment so they tend to be persistent in the environment. They have been found in air, water,soil, and sediments throughoutthe world.PCBs can enter the body through inhalation, ingestion, and dermal routes of exposure. They are readily absorbed but are slowly metabolized and excreted. In particular, PCBs initially distribute to the liver and muscle tissues, but eventually accumulate in lipid-rich tissues.
This leads to greater concentrations of PCBS in adipose tissue, breast milk, the liver, and skin. The data analysis was subsequently performed using Network Analyst, a standard web browser for network analysis and interactive exploration. Keywords TCDD, Furans, DBLCL, bioinformatics, GEO, Array Express Number of pages 59 Date of submission October,2017 Supervisor’s signature ii n ACKNOWLEDGEMENT First of all, we know that knowledge is just only can be proved by our works, and internship is one of the best opportunity for a student whose can do their first project before they find their jobs to enroll in the future. Besides that, we are not only improving ourselves by knowledge in company environment, institute or laboratory but also making more friends whose are having many experiences in environment, and it will help us in the near future.
From my perspective, this internship is absolutely needed, helpful and important. Because of that, and be assigned by the International Programs Office and also the allowed of Department of Biomedical Engineering and Environmental Sciences (National TsingHua University, Taiwan). To well done this thesis, I want to express profound gratitude to Advanced Education Program, the school administrators, the staffs in Department of Biomedical Engineering and Environmental Sciences, the staffs of YC laboratory, and particularly my supervisor,Associate. DRTran Van Dien and Prof Chun-Yu Chuang whose were always supporting me every single time I got troubles.
I would like to send both of supervisors a warmly thanks for the supporting me, and for their sacrifice for education, as same as environmental issues in Taiwan and Vietnam as all countries in the world. Finally, I would like to say that I had tried my best to finish this thesis in the best way, I guess. However, to be honest, I partly believe that my thesis still have some problems because of the limitation of knowledge and reality experiences, especially in our environmental circumstances these days. It is totally happy if I can iii n get feedbacks and comments from you, my Teachers, Professors, and Supervisors, to finish my thesis in a fantastic way, to get the best results.
Sincerely, Thai Nguyen October, 2017 THAVISACK MIVONGSACK iv n TABLE OF CONTENTS DOCUMENTATION PAGE WITH ABSTRACT. iii TABLE OF CONTENTS .v LIST OF FIGURES .ix PART I: INTRODUCTION .3 PART II:LITERATURE REVIEW. Polychlorinated Biphenyls (PCBs) Toxicity. The industrial production of PCB.
PCBs and Environment. Health Effects of PCBs. Diffuse large B cell lymphoma (DLBCL). Gene-network components .1 Gene-network database:Array Express and (GEO).
Gene network analysis and Cytoscape for gene-network analysis .24 v n PART IV: RESULTS AND DISCUSSIONS .1 Differentially expressed genes. Gene-network construction of DLBCL and PCBs .38 PART V: CONCLUSION AND RECOMMENDATION .43 vi n LIST OF FIGURES Figure 2.1: Diagram of Polychlorinated Biphenyls (PCBs)(Shoemaker, 2005) .2: Polychlorinated biphenyls – levels in foods .3: Diffuse large Bcell lymphoma .1: The flowchart of methodology.2: Cytoscape home page(Shannon P, 2003) .1: Diagram of Gene-network construction of DLBCL & PBCs Sources: (Rosenwald,2002) .2: The potential regulatory pathway of NHL progression in response to PCB exposure Source: (Miller, 2001) .38 vii n LIST OF TABLES Table 4.1: Genetics Datasets of DLBCL .2: Datasets on Array Express used for PCB analysis .3: Differentially expressed genes, including –up and down – regulate genes in Diffuse Large B cell lymphoma compared to normal cells .4: Differentially expressed genes, including up-and down – regulated genes activated by PCB compared to control group. 35 viii n ABBRIVIATION ABC Activated B cell AML Acute myeloid leukemia ALL Acute lymphoblastic leukemia B-Cells B-lymphocytes B-NHL Non Hodgkin lymphoma DLBCL Diffuse large B cell lymphoma DMSO Dimethyl sulfoxide DEGS Differentially expressed genes analysis FL Follicular lymphoma FDR False discovery rate GEO (NCBI) Gene expression omnibus National center for Biotechnology information GO Gene Ontology HL Hodgkin lymphoma HIV Human immunodeficiency virus ID Identifier IARC International agency for research on cancer MIAME Minimum information about microarray experiment MAGE-ML Microarray and Gene Expression Markup Language NPL N-acetylneuraminate pyruvate lyase NHL Non Hodgkin lymphoma PCB Polychlorinated biphenyls RS Reed-Sternberg SNPs Single Nocleotide Polymorphisms T-Cells T-lymphocytes ix n PART I: INTRODUCTION 1. Rationale Polychlorinated biphenyls, in short PCBs, are a group of man-made chemicals.PCBs have been used in many different products, including electrical equipment, surface coatings, inks, adhesives, flame-retardants, and paints.
PCBs may be released into the environment, for instance when waste that contains PCBs is incinerated or stored in landfills(Morris, 2017).PCBs are probable human carcinogens and can also cause non-cancer health effects, such as reduced ability to fight infections, low birth weights, and learning problems. The risks and hazards associated with PCBs in the Hudson River are a function of the toxicity of PCBs and an individual's exposure(Hudson, 2016).The most commonly observed health effects in people exposed to large amounts of PCBs are skin conditions such as acne and rashes. Studies in exposed workers have shown changes in blood and urine that may indicate liver damage. PCB exposures in the general population are not likely to result in skin and liver effects.
Most of the studies of health effects of PCBs in the general population examined children of mothers who were exposed to PCBs(Buford Hwy NE, 2014). Polychlorinated biphenyls (PCBs) were powerful carcinogens. A carcinogen is any substance or agent that tends to produce a cancer. Polychlorinated biphenyls are found in things such as asbestos and radon.
However, we are also forced to consume it in our foods. There are exposed to many substances at any given time. This includes those we encounter at work, school, or home, in the food we eat and in the air we breathe(Jeni, 2011). 1 n But it’s almost impossible anyone could know precisely what they’ve been exposed to.
PCBs are toxic. They can provoke serious health effects that go beyond cancer. They can also play a role in hormone disruption, reduced ability to reproduce, skin toxicity, immune system disorders. Lymphoma is the most common blood cancer that develop in lymphatic system.
The two main categories of lymphoma are Hodgkin lymphoma and non-Hodgkin lymphoma (NHL)(Ferlay, 2013). Lymphoma occurs when cells of the immune system called lymphocytes, a type of white blood cell, grow and multiply uncontrollably. Cancerous lymphocytes can travel to many parts of the body, including the lymph nodes, spleen, bone marrow, blood, or other organs, and form a mass called a tumor. The body has two main types of lymphocytes that can develop into lymphomas: B- lymphocytes (B-cells) and T-lymphocytes (T-cells).
Diffuse large cell lymphoma (DLBCL or DLBL) is a cancer of B cells, a type of white blood cell responsible for producing antibodies. It is the most common type of non-Hodgkin lymphoma among adults (Clinical, 1997), with an annual incidence of 7–8 cases per 100,000 people per year in the USA and the UK (Morton et al. This cancer occurs primarily in older individuals, with a median age of diagnosis at approximately 70 years of age (Smith et al., 2011), though it can also occur in children and young adults in rare cases(Smith at el. DLBCL is an aggressive tumor which can arise in virtually any part of the body (Kumar et al., 2009),and the first sign of this illness is typically the observation of a rapidly growing mass, sometimes associated with B symptoms: fever, weight loss, and night sweats (Freeman et al, 2012).
Objectives • The aims of the study was tosummarize the health implications associated with exposure topolychlorinatedbiphenyls (PCBs). • To identify the potential pathway exposure to dioxin corresponding to DLBCL • To express the gene number that exposure to dioxin can induce DLBCL and PCBs • To evaluate diffuse large B-cell lymphoma (DLBCL) and construct regulatory networks of genes and miRNAs to gradually reveal the underlying mechanisms of DLBCL development. 3 n PART II:LITERATURE REVIEW 2. It can cause a number of different harmfuleffects.
They are highly toxic to aquatic life and persist in the environment for long periods of time. They can accumulate in food chains and may produce harmful sideeffects at high concentrations. There are no known natural sources of PCBs in the environment. PCBs are either oilyliquids or solids and are colorless to light yellow.
Some PCBs are volatile and may exist as avapor in air. They have no known smell or taste(Buford Hwy NE, 2014). PCBs enter the environment as mixturescontaining a variety of individual chlorinated biphenyl components, known as congeners, as wellas impurities. Because the health effects of environmental mixtures of PCBs are difficult toevaluate, most of the information in thistoxicological profile is about seven types of PCBmixtures that were commercially produced.
These seven kinds of PCB mixtures include 35% ofall the PCBs commercially produced and 98% of PCBs sold in the United States since 1970.Some commercial PCB mixtures are known in the United States by their industrial trade name,Aroclor. For example, the name Aroclor 1254 means that the mixture contains approximately54% chlorine by weight, as indicated by the second two digits in the name. Because they do not burn easily and are good insulating materials, PCBs were used widely as coolants and lubricantsin transformers, capacitors, and other electrical equipment. The manufacture of PCBs stopped inthe 4 n United States in August 1977 because there was evidence that PCBs build up in theenvironment and may cause harmful effects.
Consumer products that may contain PCBs includeold fluorescent lighting fixtures, electrical devices or appliances containing PCB capacitors madebefore PCB use was stopped, old microscope oil, and old hydraulic oil. Polychlorinated Biphenyls (PCBs) Toxicity Since PCBs are found throughout the environment, it is likely that everyone has been exposed to them. PCBs can enter the body by eating or drinking contaminated food, through the air we breathe, or by skin contact. PCBs are easily absorbed by the body and are stored in fatty tissue.
PCBs are not eliminated well, so they can accumulate in the body (Gray et al.,2003; Thrasher and Crawley, 2009).