Histone modifications and respiratory effects of traffic particle exposure

Summary

Principal Investigator: Lifang Hou
Abstract: DESCRIPTION (provided by applicant): Air pollution is a major public health concern, accounting for ~800,000 annual deaths. Exposure to air particulate matter (PM) has been shown to reduce lung function and increase respiratory disease rates. Inhaled PM can up-regulate systemic inflammatory responses in blood, which play important roles in PM- related lung function reduction and respiratory diseases. Blood leukocyte gene expression profiling in highly PM-exposed subjects has revealed that systemic inflammatory responses in blood are mediated by extensive gene expression shifts. This observation provides a tremendous opportunity to develop new biomarkers that are related to gene expression regulation. Histones are nuclear globular proteins that can be covalently modified by the addition of methyl, acetyl, and other chemical groups, which are inducible by certain inflammatory mediators, thus influencing chromatin structure and gene expression. Exposure to environmental pollutants has been shown to induce histone modifications in vitro. We recently observed increases in two of such modifications, i.e., H3K4 dimethylation and H3K9 acetylation, in blood leukocytes from a highly PM- exposed population. We hypothesize that ambient PM exposure may cause blood leukocyte histone modifications in response to PM-induced systemic inflammation. Such histone modifications may shift blood leukocyte gene expression toward profiles promoting further systemic inflammatory responses that, in turn, adversely affect lung function. We propose to test these hypotheses using data and biospecimens from our recently completed Beijing Truck Driver Air Pollution Study (BTDAS) in Beijing, China, one of the most polluted cities in the world. Sixty truck drivers (high exposure) and 60 indoor workers (low exposure) were recruited. We used personal air monitors and urine biomarkers to measure exposure to PM2.5, its toxic metals, and traffic exhausts on two independent work days with 1-2 week intervals. We collected after-work blood samples and lung function data, and measured inflammation markers. We propose to conduct an ancillary study to examine whether personal PM2.5 and its metal components are associated with histone modifications found to be induced by PM-contained metals in previous experimental studies;and whether PM-related histone modifications are associated with plasma inflammatory mediators) and/or lung function. We will replicate our findings from BTDAS in traffic-exposed police officers and referents in Milan, Italy, with PM2.5 levels typical of large cities in Europe/North America. Replication in a population with relatively lower exposure and different ethnicity will permit to test generalizability. The proposed study is highly time- and cost-effective and the first to examine the role of histone modifications in air pollution-related lung function reduction. Our results will offer a new researh area for future investigations on the role of histone modifications in PM-related lung function reduction. If we observed the hypothesized associations, we will seek funding to expand this line of research in large-scale studies in populations with lower exposure such as the US populations.
Funding Period: 2012-09-14 - 2014-08-31
more information: NIH RePORT

Top Publications

  1. pmc Inhalable particulate matter and mitochondrial DNA copy number in highly exposed individuals in Beijing, China: a repeated-measure study
    Lifang Hou
    Department of Preventive Medicine Feinberg, School of Medicine Northwestern University, Chicago, IL 60611, USA
    Part Fibre Toxicol 10:17. 2013
  2. ncbi Environmental and occupational exposure to chemicals and telomere length in human studies
    Xiao Zhang
    Department of Preventive Medicine, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA
    Occup Environ Med 70:743-9. 2013
  3. pmc Evolutionary age of repetitive element subfamilies and sensitivity of DNA methylation to airborne pollutants
    Hyang Min Byun
    Laboratory of Environmental Epigenetics, Exposure Epidemiology and Risk Program, Harvard School of Public Health, Boston, MA, USA
    Part Fibre Toxicol 10:28. 2013
  4. doi Environmental and occupational exposure to chemicals and telomere length in human studies
    Xiao Zhang
    Department of Preventive Medicine, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA
    Postgrad Med J 89:722-8. 2013
  5. pmc Altered methylation in tandem repeat element and elemental component levels in inhalable air particles
    Lifang Hou
    Department of Preventive Medicine, Feinberg School of Medicine, Northwestern University, Chicago, Illinois The Robert H Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, Illinois
    Environ Mol Mutagen 55:256-65. 2014
  6. ncbi Effects of short-term exposure to inhalable particulate matter on DNA methylation of tandem repeats
    Liqiong Guo
    Laboratory of Environmental Epigenetics, Department of Environmental Health, Harvard School of Public Health, Boston, Massachusetts Key Laboratory of Pollution Processes and Environmental Criteria Ministry of Education, College of Environmental Sciences and Engineering, Nankai University, Tianjin, China
    Environ Mol Mutagen 55:322-35. 2014

Research Grants

Detail Information

Publications6

  1. pmc Inhalable particulate matter and mitochondrial DNA copy number in highly exposed individuals in Beijing, China: a repeated-measure study
    Lifang Hou
    Department of Preventive Medicine Feinberg, School of Medicine Northwestern University, Chicago, IL 60611, USA
    Part Fibre Toxicol 10:17. 2013
    ..Mitochondrial DNA copy number (MtDNAcn) is a marker of mitochondrial damage and malfunctioning. We evaluated whether ambient PM exposure affects MtDNAcn in a highly-exposed population in Beijing, China...
  2. ncbi Environmental and occupational exposure to chemicals and telomere length in human studies
    Xiao Zhang
    Department of Preventive Medicine, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA
    Occup Environ Med 70:743-9. 2013
    ....
  3. pmc Evolutionary age of repetitive element subfamilies and sensitivity of DNA methylation to airborne pollutants
    Hyang Min Byun
    Laboratory of Environmental Epigenetics, Exposure Epidemiology and Risk Program, Harvard School of Public Health, Boston, MA, USA
    Part Fibre Toxicol 10:28. 2013
    ..The purpose of the study is to evaluate sensitivity of DNA methylation in differentially‒evolved LINE, Alu, and HERV subfamilies to different types of airborne pollutants...
  4. doi Environmental and occupational exposure to chemicals and telomere length in human studies
    Xiao Zhang
    Department of Preventive Medicine, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA
    Postgrad Med J 89:722-8. 2013
    ....
  5. pmc Altered methylation in tandem repeat element and elemental component levels in inhalable air particles
    Lifang Hou
    Department of Preventive Medicine, Feinberg School of Medicine, Northwestern University, Chicago, Illinois The Robert H Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, Illinois
    Environ Mol Mutagen 55:256-65. 2014
    ..115, 95% CI: 0.034; 0.196, FDR = 0.042). PM-associated differences in blood tandem-repeat methylation may help detect biological effects of the exposure and identify individuals who may eventually experience higher lung cancer risk...
  6. ncbi Effects of short-term exposure to inhalable particulate matter on DNA methylation of tandem repeats
    Liqiong Guo
    Laboratory of Environmental Epigenetics, Department of Environmental Health, Harvard School of Public Health, Boston, Massachusetts Key Laboratory of Pollution Processes and Environmental Criteria Ministry of Education, College of Environmental Sciences and Engineering, Nankai University, Tianjin, China
    Environ Mol Mutagen 55:322-35. 2014
    ..Measuring tandem-repeat hypomethylation in easy-to-obtain blood specimens might identify individuals with biological effects and potential cancer risk from PM exposure...

Research Grants30

  1. Comparative Mechanisms of Cancer Chemoprevention
    Roderick H Dashwood; Fiscal Year: 2013
    ..This application is innovative and timely in bridging basic mechanisms, preclinical models, and human studies of epigenetics and diet. ..
  2. Integrating Structive Activity, Biokinetics and Response for ENP Risk Assessment
    Brian D Thrall; Fiscal Year: 2013
    ....
  3. Molecular Regulation of Mammalian Meiosis
    Kenneth Paigen; Fiscal Year: 2013
    ..Results of the program project will significantly increase the understanding of the mechanisms that regulate meiosis as well as their involvement in other important biological processes. ..
  4. Overall Application: Trauma Primes Cells
    Anirban Banerjee; Fiscal Year: 2013
    ....
  5. Novel Methods to Assess the Effects of Chemicals on Child Development
    Susan L Schantz; Fiscal Year: 2013
    ..This Center's research will fill an important gap in our knowledge by investigating the effects of these chemicals, both alone and combination with a high fat diet on reproductive and neural development. ..
  6. Air Pollution, Epigenetics and Cardiovascular Health: A Human Intervention Trial
    Andrea Baccarelli; Fiscal Year: 2013
    ....
  7. Elucidating Loci Involved in Prostate Cancer Suceptibility
    Brian E Henderson; Fiscal Year: 2013
    ..The overarching goal is to discover the pathways that drive prostate cancer pathogenesis and to assess their role in clinical decision making. ..
  8. TOXIC SUBSTANCES IN THE ENVIRONMENT
    Martyn T Smith; Fiscal Year: 2013
    ..The program will be overseen and coordinated by an Administration core (A). ..
  9. EPIDEMIOLOGY OF ALCOHOL PROBLEMS
    Thomas K Greenfield; Fiscal Year: 2013
    ..We plan to build research capacity in the Center and other organizations, enhance careers of new investigators, and make key findings accessible to researchers, policy makers, practitioners, and the public. ..
  10. Pacific NorthWest Regional Center of Excellence (PNWRCE)
    Jay A Nelson; Fiscal Year: 2013
    ..pseudomallei host pathogen response during both the septicemic as well as the intracellular phases of the disease. ..
  11. NUCLEAR STRUCTURE AND GENE EXPRESSION
    Janet L Stein; Fiscal Year: 2013
    ..abstract_text> ..
  12. Northeast Biodefense Center
    W Ian Lipkin; Fiscal Year: 2013
    ..As a Center based in a School of Public Health and a State Department of Health, the NBC has a firm commitment to and practical understanding of Emergency Preparedness. ..
  13. The Cardiopulmonary Effects of Particulate Exposure
    David C Christiani; Fiscal Year: 2013
    ..5 <m (PM2.5). We have focused on particles from fossil fuel power plants and welding as a model to evaluate the cardiovascular and systemic inflammatory health effects of metallic particles. ..
  14. Elucidating Risks: From Exposure and Mechanism to Outcome
    James A Swenberg; Fiscal Year: 2013
    ..This Program is highly relevant to Superfund by addressing high-priority chemicals and by focusing on mechanisms underlying health effects, exposure assessment, and remediation to mitigate exposure and toxicity. ..
  15. Superfund Metal Mixtures, Biomarkers and Neurodevelopment
    David C Bellinger; Fiscal Year: 2013
    ..Aim 4- To promote rapid dissemination of significant research findings;and Aim 5- Compliance- To ensure compliance with NIH requirements for data and resource-sharing and the human and animal institutional review board requirements ..
  16. Enviromental Exposures, Host Factors and Human Disease
    Frank D Gilliland; Fiscal Year: 2013
    ..The Center is poised to advance research in these areas by building on its successful approaches in facilitating cutting-edge environmental health science research. ..
  17. Hopkins Center for Eliminate Cardiovascular Health Disparities
    Lisa A Cooper; Fiscal Year: 2013
    ..abstract_text> ..
  18. PAHs: New Technologies and Emerging Health Risks
    David E Williams; Fiscal Year: 2013
    ..Accomplishing these goals will provide significant scientific advancement and improve the quality of life for impacted communities. ..