Elucidating Risks: From Exposure and Mechanism to Outcome

Summary

Principal Investigator: James A Swenberg
Abstract: DESCRIPTION (provided by applicant): The UNC-CH Program's multidisciplinary research will address scientific issues that underpin the assessment and reduction of risks to human health associated with high priority chemicals at Superfund sites. The overall specific aims are to improve the scientific foundation for risk assessment, elucidate mechanisms responsible for inter-individual susceptibility, advance approaches to assessing exposure to hazardous chemicals, and more efficiently reduce risks by remediation of hazardous waste sites. In this competing continuation, we will focus on three major classes of chemicals ~ polycyclic aromatic hydrocarbons (PAHs), halogenated hydrocarbons, and heavy metals ~ in three biomedical and two non-biomedical projects, two Research Support Cores, a Research Translation Core (RTC), and an Administrative Core. Research themes that cross multiple projects and cores include: (1) developing biomarkers of exposure and effect for human and experimental models of environmental disease over a range of exposure levels to improve low-dose quantitative risk assessment;(2) applying new molecular tools in a systems biology framework to understand metabolic pathways critical for environmental disease, predict in vivo inter-individual differences in susceptibility and risk, and evaluate complex microbial communities in bioremediation systems;(3) using advanced analytical tools to identify mechanisms of genotoxicity;(4) using advanced statistical and bioinformatics methods to evaluate gene-environment interactions;and (5) quantifying the chronic exposure and bioavailability of toxic compounds in environmental systems. This work will also be integrated by sharing methods and resources across projects and cores, by regular meetings of all researchers, and by co-advising of trainees by faculty in different projects and cores. Working with investigators, the RTC will enhance the capacity of government agencies to provide technical assistance to communities, develop improved decision-support tools, and promote the commercialization of our research products. 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.
Funding Period: 1997-04-01 - 2016-03-31
more information: NIH RePORT

Top Publications

  1. pmc Role of epigenetic aberrations in the development and progression of human hepatocellular carcinoma
    Igor P Pogribny
    Division of Biochemical Toxicology, National Center for Toxicological Research, Jefferson, AR 72079, United States Electronic address
    Cancer Lett 342:223-30. 2014
  2. pmc Cosolvent flushing for the remediation of PAHs from former manufactured gas plants
    P Schultz Birak
    Department of Environmental Sciences and Engineering, University of North Carolina, Chapel Hill, NC 27599 7431, USA
    J Contam Hydrol 126:72-84. 2011
  3. pmc Tet proteins can convert 5-methylcytosine to 5-formylcytosine and 5-carboxylcytosine
    Shinsuke Ito
    Howard Hughes Medical Institute and Department of Biochemistry and Biophysics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599 7295, USA
    Science 333:1300-3. 2011
  4. pmc Genotoxicity in Atlantic killifish (Fundulus heteroclitus) from a PAH-contaminated Superfund site on the Elizabeth River, Virginia
    Dawoon Jung
    Nicholas School of Environment, Duke University, Box 90328, Durham, NC 27708 0328, USA
    Ecotoxicology 20:1890-9. 2011
  5. ncbi Synthesis of uniformly 13C-labeled polycyclic aromatic hydrocarbons
    Zhenfa Zhang
    Department of Environmental Sciences and Engineering, CB7431, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA
    Org Biomol Chem 9:5431-5. 2011
  6. pmc MicroRNA expression in the livers of inbred mice
    Daniel M Gatti
    Department of Environmental Sciences and Engineering, University of North Carolina, Chapel Hill, NC 27599, USA
    Mutat Res 714:126-33. 2011
  7. ncbi Stable-isotope probing of the polycyclic aromatic hydrocarbon-degrading bacterial guild in a contaminated soil
    Maiysha D Jones
    Department of Environmental Sciences and Engineering, Gillings School of Global Public Health, The University of North Carolina at Chapel Hill, CB 7431 Chapel Hill, NC 27599 7431, USA
    Environ Microbiol 13:2623-32. 2011
  8. pmc Increased incidence of aflatoxin B1-induced liver tumors in hepatitis virus C transgenic mice
    Emmanuelle Jeannot
    Department of Environmental Sciences and Engineering, University of North Carolina, Chapel Hill, NC 27599 7431, USA
    Int J Cancer 130:1347-56. 2012
  9. pmc Stable isotope probing of an algal bloom to identify uncultivated members of the Rhodobacteraceae associated with low-molecular-weight polycyclic aromatic hydrocarbon degradation
    Tony Gutierrez
    Lancaster University, Lancaster Environment Centre, Lancaster LA14YQ, United Kingdom
    Appl Environ Microbiol 77:7856-60. 2011
  10. pmc Desorption and bioavailability of polycyclic aromatic hydrocarbons in contaminated soil subjected to long-term in situ biostimulation
    Stephen D Richardson
    Gillings School of Global Public Health, University of North Carolina, Chapel Hill, North Carolina, USA
    Environ Toxicol Chem 30:2674-81. 2011

Research Grants

  1. EPIDEMIOLOGY OF ALCOHOL PROBLEMS
    Thomas K Greenfield; Fiscal Year: 2013

Detail Information

Publications175 found, 100 shown here

  1. pmc Role of epigenetic aberrations in the development and progression of human hepatocellular carcinoma
    Igor P Pogribny
    Division of Biochemical Toxicology, National Center for Toxicological Research, Jefferson, AR 72079, United States Electronic address
    Cancer Lett 342:223-30. 2014
    ....
  2. pmc Cosolvent flushing for the remediation of PAHs from former manufactured gas plants
    P Schultz Birak
    Department of Environmental Sciences and Engineering, University of North Carolina, Chapel Hill, NC 27599 7431, USA
    J Contam Hydrol 126:72-84. 2011
    ..Fitted mass-transfer rates were two to three orders of magnitude lower than predicted values based on published data using artificially contaminated sands...
  3. pmc Tet proteins can convert 5-methylcytosine to 5-formylcytosine and 5-carboxylcytosine
    Shinsuke Ito
    Howard Hughes Medical Institute and Department of Biochemistry and Biophysics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599 7295, USA
    Science 333:1300-3. 2011
    ..Thus, we identify two previously unknown cytosine derivatives in genomic DNA as the products of Tet proteins. Our study raises the possibility that DNA demethylation may occur through Tet-catalyzed oxidation followed by decarboxylation...
  4. pmc Genotoxicity in Atlantic killifish (Fundulus heteroclitus) from a PAH-contaminated Superfund site on the Elizabeth River, Virginia
    Dawoon Jung
    Nicholas School of Environment, Duke University, Box 90328, Durham, NC 27708 0328, USA
    Ecotoxicology 20:1890-9. 2011
    ..Using similar LC-MS/MS methods, we found no evidence that oxidative DNA adducts had a role in observed genotoxicity...
  5. ncbi Synthesis of uniformly 13C-labeled polycyclic aromatic hydrocarbons
    Zhenfa Zhang
    Department of Environmental Sciences and Engineering, CB7431, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA
    Org Biomol Chem 9:5431-5. 2011
    ..All target products were obtained in excellent yields, including the alternant PAH U-(13)C-naphthalene, U-(13)C-phenanthrene, U-(13)C-anthracene, U-(13)C-benz[a]anthracene, U-(13)C-pyrene and the nonalternant PAH U-(13)C-fluoranthene...
  6. pmc MicroRNA expression in the livers of inbred mice
    Daniel M Gatti
    Department of Environmental Sciences and Engineering, University of North Carolina, Chapel Hill, NC 27599, USA
    Mutat Res 714:126-33. 2011
    ....
  7. ncbi Stable-isotope probing of the polycyclic aromatic hydrocarbon-degrading bacterial guild in a contaminated soil
    Maiysha D Jones
    Department of Environmental Sciences and Engineering, Gillings School of Global Public Health, The University of North Carolina at Chapel Hill, CB 7431 Chapel Hill, NC 27599 7431, USA
    Environ Microbiol 13:2623-32. 2011
    ....
  8. pmc Increased incidence of aflatoxin B1-induced liver tumors in hepatitis virus C transgenic mice
    Emmanuelle Jeannot
    Department of Environmental Sciences and Engineering, University of North Carolina, Chapel Hill, NC 27599 7431, USA
    Int J Cancer 130:1347-56. 2012
    ..In summary, HCV proteins core, E1, E2 and p7 are sufficient to reproduce the cocarcinogenic effect of HCV and AFB1, which is a known clinical phenomenon...
  9. pmc Stable isotope probing of an algal bloom to identify uncultivated members of the Rhodobacteraceae associated with low-molecular-weight polycyclic aromatic hydrocarbon degradation
    Tony Gutierrez
    Lancaster University, Lancaster Environment Centre, Lancaster LA14YQ, United Kingdom
    Appl Environ Microbiol 77:7856-60. 2011
    ..As demonstrated by this work, the application of uniformly ¹³C-labeled PAHs in SIP experiments can successfully be used to identify novel PAH-degrading bacteria in marine waters...
  10. pmc Desorption and bioavailability of polycyclic aromatic hydrocarbons in contaminated soil subjected to long-term in situ biostimulation
    Stephen D Richardson
    Gillings School of Global Public Health, University of North Carolina, Chapel Hill, North Carolina, USA
    Environ Toxicol Chem 30:2674-81. 2011
    ....
  11. pmc The utility of naphthyl-keratin adducts as biomarkers for jet-fuel exposure
    Juei Chuan C Kang-Sickel
    Department of Environmental Sciences and Engineering, Gillings School of Global Public Health, The University of North Carolina at Chapel Hill, USA
    Biomarkers 16:590-9. 2011
    ..Further studies are warranted to characterize the relationship between NKA, other exposure biomarkers, and/or biomarkers of biological effects due to naphthalene and/or PAH exposure...
  12. pmc Computational tools for discovery and interpretation of expression quantitative trait loci
    Fred A Wright
    Department of Biostatistics, University of North Carolina, Chapel Hill, NC 27599, USA
    Pharmacogenomics 13:343-52. 2012
    ..The purpose of this review is to help investigators find appropriate programs for eQTL analysis and interpretation...
  13. pmc Integrating address geocoding, land use regression, and spatiotemporal geostatistical estimation for groundwater tetrachloroethylene
    Kyle P Messier
    Department of Environmental Science and Engineering, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC, USA
    Environ Sci Technol 46:2772-80. 2012
    ..The LUR model shows significant influence of dry cleaners at short ranges. The integration of the LUR model as mean trend in BME results in a 7.5% decrease in cross validation mean square error compared to BME with a constant mean trend...
  14. pmc Mechanistic considerations for human relevance of cancer hazard of di(2-ethylhexyl) phthalate
    Ivan Rusyn
    Department of Environmental Sciences and Engineering, University of North Carolina, Chapel Hill, NC 27599 7431, USA
    Mutat Res 750:141-58. 2012
    ..g., liver and testis) in rats and mice can not be ruled out and DEHP was classified as possibly carcinogenic to humans (Group 2B)...
  15. pmc Formation of hydroxymethyl DNA adducts in rats orally exposed to stable isotope labeled methanol
    Kun Lu
    Department of Environmental Sciences and Engineering, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA
    Toxicol Sci 126:28-38. 2012
    ....
  16. pmc Use of LC-MS/MS and stable isotopes to differentiate hydroxymethyl and methyl DNA adducts from formaldehyde and nitrosodimethylamine
    Kun Lu
    Department of Environmental Sciences and Engineering, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA
    Chem Res Toxicol 25:664-75. 2012
    ..The use of highly sensitive LC-MS/MS and isotope labeled compounds for exposure solves these challenges and provides mechanistic insights on the formation and role of these DNA adducts...
  17. pmc Porticoccus hydrocarbonoclasticus sp. nov., an aromatic hydrocarbon-degrading bacterium identified in laboratory cultures of marine phytoplankton
    Tony Gutierrez
    Department of Environmental Sciences and Engineering, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, North Carolina, USA
    Appl Environ Microbiol 78:628-37. 2012
    ....
  18. pmc Mobilization of manufactured gas plant tar with alkaline flushing solutions
    Scott C Hauswirth
    Department of Environmental Sciences and Engineering, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States
    Environ Sci Technol 46:426-33. 2012
    ..Such an approach may have practical applications and would be significantly less expensive than surfactant-based methods...
  19. pmc Arsenic in North Carolina: public health implications
    Alison P Sanders
    Department of Environmental Sciences and Engineering, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, United States
    Environ Int 38:10-6. 2012
    ..This study reveals relevant information on the location of arsenic-contaminated private domestic wells in North Carolina and indicates potential areas at increased risk for adverse health outcomes...
  20. pmc Multiple DNA extractions coupled with stable-isotope probing of anthracene-degrading bacteria in contaminated soil
    Maiysha D Jones
    Department of Environmental Sciences and Engineering, The University of North Carolina at Chapel Hill, CB 7431, Chapel Hill, North Carolina 27599 7431, USA
    Appl Environ Microbiol 77:2984-91. 2011
    ....
  21. pmc Pyrosequence analysis of bacterial communities in aerobic bioreactors treating polycyclic aromatic hydrocarbon-contaminated soil
    David R Singleton
    Department of Environmental Sciences and Engineering, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC 27599 7431, USA
    Biodegradation 22:1061-73. 2011
    ....
  22. pmc Benzene, the exposome and future investigations of leukemia etiology
    Martyn T Smith
    Genes and Environment Laboratory, School of Public Health, University of California, Berkeley, CA 94720 7356, USA
    Chem Biol Interact 192:155-9. 2011
    ..We propose that we should attempt to characterize the 'exposome' of human leukemia by using unbiased laboratory-based methods to find the unknown 'environmental' factors that contribute to leukemia etiology...
  23. pmc Accumulation of true single strand breaks and AP sites in base excision repair deficient cells
    April M Luke
    Curriculum in Toxicology, University of North Carolina, Chapel Hill, USA
    Mutat Res 694:65-71. 2010
    ..Furthermore, the Pol β-null cells displayed greater AP site formation than the parental DT40 cells. OTX use represents a facile approach for assessing SSB formation, whose benefits can also be applied to other established SSB assays...
  24. pmc Convenient, multi-well plate-based DNA damage response analysis using DT40 mutants is applicable to a high-throughput genotoxicity assay with characterization of modes of action
    John R Ridpath
    Department of Environmental Sciences and Engineering, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599 7431, USA
    Environ Mol Mutagen 52:153-60. 2011
    ....
  25. pmc Comparative analysis of promoter methylation and gene expression endpoints between tumorous and non-tumorous tissues from HCV-positive patients with hepatocellular carcinoma
    Eric J Formeister
    Department of Environmental Sciences and Engineering, University of North Carolina, Chapel Hill, NC, USA
    Mutat Res 692:26-33. 2010
    ..The finding that RIZ1 methylation and increased levels of LINE-1 hypomethylation in non-tumorous tissues are associated with time to recurrence underscores the importance of assessing the epigenetic state of the liver remnant...
  26. pmc Effects of nonionic surfactant addition on populations of polycyclic aromatic hydrocarbon-degrading bacteria in a bioreactor treating contaminated soil
    Hongbo Zhu
    Department of Environmental Sciences and Engineering, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, North Carolina 27599 7431, USA
    Environ Sci Technol 44:7266-71. 2010
    ..These results indicate that surfactant addition can have substantial, differential effects on populations of organisms responsible for contaminant degradation within a microbial community...
  27. pmc Toxicogenetics: population-based testing of drug and chemical safety in mouse models
    Ivan Rusyn
    Department of Environmental Sciences and Engineering, 0031 Michael Hooker Research Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
    Pharmacogenomics 11:1127-36. 2010
    ....
  28. pmc Bayesian maximum entropy integration of ozone observations and model predictions: an application for attainment demonstration in North Carolina
    Audrey de Nazelle
    University of North Carolina, Chapel Hill, North Carolina, USA
    Environ Sci Technol 44:5707-13. 2010
    ..We show that the BME data integration approach, compared to a spatial interpolation of measured data, improves the accuracy and the precision of ozone estimations across the state...
  29. pmc Surfactant-enhanced desorption and biodegradation of polycyclic aromatic hydrocarbons in contaminated soil
    Hongbo Zhu
    Department of Environmental Sciences and Engineering, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, North Carolina 27599 7431, USA
    Environ Sci Technol 44:7260-5. 2010
    ....
  30. pmc Biomarker variance component estimation for exposure surrogate selection and toxicokinetic inference
    Jon R Sobus
    Human Exposure and Atmospheric Sciences Division, National Exposure Research Laboratory, Office of Research and Development, U S Environmental Protection Agency, 109 T W Alexander Drive, Research Triangle Park, NC 27711, USA
    Toxicol Lett 199:247-53. 2010
    ..The methods described in this analysis should be considered for the selection and interpretation of biomarkers as exposure surrogates in future exposure investigations...
  31. pmc Use of in vitro HTS-derived concentration-response data as biological descriptors improves the accuracy of QSAR models of in vivo toxicity
    Alexander Sedykh
    Laboratory for Molecular Modeling, Division of Medicinal Chemistry and Natural Products, U S Environmental Protection Agency, Research Triangle Park, North Carolina, USA
    Environ Health Perspect 119:364-70. 2011
    ..Hundreds of chemicals have been tested in dozens of cell lines across extensive concentration ranges by the National Toxicology Program in collaboration with the National Institutes of Health Chemical Genomics Center...
  32. pmc Interstrain differences in the liver effects of trichloroethylene in a multistrain panel of inbred mice
    Blair U Bradford
    Department of Environmental Sciences and Engineering, University of North Carolina, Chapel Hill, North Carolina 27599, USA
    Toxicol Sci 120:206-17. 2011
    ..These studies provide better understanding of the mechanisms of TCE-induced toxicity anchored on metabolism and genotype-phenotype correlations that may define susceptibility or resistance...
  33. pmc Determination of N2-hydroxymethyl-dG adducts in the nasal epithelium and bone marrow of nonhuman primates following 13CD2-formaldehyde inhalation exposure
    Benjamin C Moeller
    Curriculum in Toxicology, University of North Carolina, Chapel Hill, North Carolina 27599 7431, United States
    Chem Res Toxicol 24:162-4. 2011
    ..In contrast, only endogenous adducts were detectable in the bone marrow, even though ∼10 times more DNA was analyzed...
  34. pmc Chronic administration of ethanol leads to an increased incidence of hepatocellular adenoma by promoting H-ras-mutated cells
    Emmanuelle Jeannot
    Department of Environmental Sciences and Engineering, University of North Carolina, Chapel Hill, 27599 7431, United States
    Cancer Lett 301:161-7. 2011
    ..We show that ethanol does not cause detectable oxidative stress in the liver at any time point and acts by promoting H-ras mutated cells...
  35. pmc Endogenous versus exogenous DNA adducts: their role in carcinogenesis, epidemiology, and risk assessment
    James A Swenberg
    Department of Environmental Sciences and Engineering, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, North Carolina 27599, USA
    Toxicol Sci 120:S130-45. 2011
    ..Finally, it extends the thought process to VC, EO, and additional areas of potential research, pointing out needs, nuances, and potential paths forward to improved understanding that will lead to strong science-based risk assessment...
  36. pmc Recovery of phenanthrene-degrading bacteria after simulated in situ persulfate oxidation in contaminated soil
    Stephen D Richardson
    Department of Environmental Sciences and Engineering, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
    Environ Sci Technol 45:719-25. 2011
    ....
  37. pmc Molecular dosimetry of N2-hydroxymethyl-dG DNA adducts in rats exposed to formaldehyde
    Kun Lu
    Department of Environmental Sciences and Engineering, University of North Carolina, Chapel Hill, North Carolina 27599, United States
    Chem Res Toxicol 24:159-61. 2011
    ..In contrast, exogenous adducts were not detectable in the bone marrow of rats exposed to 15.2 ppm [(13)CD(2)] formaldehyde...
  38. pmc Global gene expression profiling of a population exposed to a range of benzene levels
    Cliona M McHale
    School of Public Health, University of California Berkeley, Berkeley, California 64720, USA
    Environ Health Perspect 119:628-34. 2011
    ..Previously, we identified genes and pathways associated with exposure to high (> 10 ppm) levels of benzene through transcriptomic analyses of blood cells from a small number of occupationally exposed workers...
  39. pmc Epigenetic alterations in liver of C57BL/6J mice after short-term inhalational exposure to 1,3-butadiene
    Igor Koturbash
    Division of Biochemical Toxicology, National Center for Toxicological Research, U S Food and Drug Administration, Jefferson, Arkansas, USA
    Environ Health Perspect 119:635-40. 2011
    ..1,3-Butadiene (BD) is a high-volume industrial chemical and a known human carcinogen. The main mode of BD carcinogenicity is thought to involve formation of genotoxic epoxides...
  40. pmc Sex-specific gene expression in the BXD mouse liver
    Daniel M Gatti
    Department of Environmental Sciences and Engineering, University of North Carolina, Chapel Hill, North Carolina 27599, USA
    Physiol Genomics 42:456-68. 2010
    ..This study enhances our understanding of sex differences at the genome level and between species, as well as increasing our knowledge of the molecular underpinnings of sex differences in responses to xenobiotics...
  41. ncbi Long-term simulation of in situ biostimulation of polycyclic aromatic hydrocarbon-contaminated soil
    Stephen D Richardson
    Department of Environmental Sciences and Engineering, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
    Biodegradation 23:621-33. 2012
    ..This study demonstrated that the presence of oxygen was the limiting factor in PAH removal, as opposed to the abundance and/or activity of PAH-degrading bacteria once oxygen reached a previously anoxic zone...
  42. pmc Cadmium exposure and the epigenome: Exposure-associated patterns of DNA methylation in leukocytes from mother-baby pairs
    Alison P Sanders
    Department of Environmental Sciences and Engineering Gillings School of Global Public Health University of North Carolina Chapel Hill, NC USA
    Epigenetics 9:212-21. 2014
    ..This study provides evidence for distinct patterns of DNA methylation or "footprints" in fetal and maternal DNA associated with exposure to Cd. ..
  43. pmc Assessment of beating parameters in human induced pluripotent stem cells enables quantitative in vitro screening for cardiotoxicity
    Oksana Sirenko
    Molecular Devices LLC, Sunnyvale, CA 94089, USA Electronic address
    Toxicol Appl Pharmacol 273:500-7. 2013
    ..These data and analysis methods may be used widely for compound screening and early safety evaluation in drug development...
  44. pmc Dosimetry of N⁶-formyllysine adducts following [¹³C²H₂]-formaldehyde exposures in rats
    Bahar Edrissi
    Department of Biological Engineering, Center for Environmental Health Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts, 02139, United States
    Chem Res Toxicol 26:1421-3. 2013
    ..1 ppm formaldehyde exposure resulting in one-third of the total load of N⁶-formyllysine being derived from exogenous sources. The results parallel previous studies of formaldehyde-induced DNA adducts...
  45. pmc Variant ALDH2 is associated with accelerated progression of bone marrow failure in Japanese Fanconi anemia patients
    Asuka Hira
    Laboratory of DNA Damage Signaling, Department of Late Effects Studies, Radiation Biology Center, Kyoto University, Kyoto, Japan
    Blood 122:3206-9. 2013
    ..Our current data indicate that the level of ALDH2 activity impacts pathogenesis in FA, suggesting the possibility of a novel therapeutic approach. ..
  46. pmc Trichloroethylene: Mechanistic, epidemiologic and other supporting evidence of carcinogenic hazard
    Ivan Rusyn
    University of North Carolina, Chapel Hill, NC, USA Electronic address
    Pharmacol Ther 141:55-68. 2014
    ..In all, consideration of the multiple evidence streams presented herein informed the IARC conclusions regarding the carcinogenicity of TCE...
  47. pmc A systematic approach for identifying and presenting mechanistic evidence in human health assessments
    Mary E Kushman
    Department of Environmental Sciences and Engineering, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States
    Regul Toxicol Pharmacol 67:266-77. 2013
    ..This approach contributes to human health assessment by effectively managing a large volume of literature, improving transparency, and facilitating subsequent synthesis of information across studies. ..
  48. ncbi A neutral glyoxal gel electrophoresis method for the detection and semi-quantitation of DNA single-strand breaks
    Brian Pachkowski
    Department of Environmental Sciences and Engineering, University of North Carolina, Chapel Hill, NC, USA
    Methods Mol Biol 1054:133-43. 2013
    ....
  49. pmc Mechanisms of HCV-induced liver cancer: what did we learn from in vitro and animal studies?
    Ivan Rusyn
    Department of Environmental Sciences and Engineering, University of North Carolina, Chapel Hill, NC 27599, USA Electronic address
    Cancer Lett 345:210-5. 2014
    ....
  50. pmc Polycyclic aromatic hydrocarbon degradation of phytoplankton-associated Arenibacter spp. and description of Arenibacter algicola sp. nov., an aromatic hydrocarbon-degrading bacterium
    Tony Gutierrez
    Department of Environmental Sciences and Engineering, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, North Carolina, USA
    Appl Environ Microbiol 80:618-28. 2014
    ....
  51. pmc Genetic and epigenetic changes in fibrosis-associated hepatocarcinogenesis in mice
    Grace Chappell
    Department of Environmental Sciences and Engineering, University of North Carolina, Chapel Hill, NC
    Int J Cancer 134:2778-88. 2014
    ..In summary, our results suggest that epigenetic events, rather than mutations in known cancer-related genes, play a prominent role in increased incidence of liver tumors in this mouse model of fibrosis-associated liver cancer...
  52. pmc Formaldehyde-associated changes in microRNAs: tissue and temporal specificity in the rat nose, white blood cells, and bone marrow
    Julia E Rager
    Department of Environmental Sciences and Engineering, Gillings School of Global Public Health, The University of North Carolina, Chapel Hill, North Carolina 27599
    Toxicol Sci 138:36-46. 2014
    ..These data inform our current hypothesis that formaldehyde-induced inflammatory signals originating in the nose may drive WBC effects. ..
  53. pmc The endogenous exposome
    Jun Nakamura
    University of North Carolina, Chapel Hill, NC, United States
    DNA Repair (Amst) 19:3-13. 2014
    ..These data provide much needed information to impact quantitative risk assessments, in the hope of moving towards the use of science, rather than default assumptions. ..
  54. ncbi Are urinary PAHs biomarkers of controlled exposure to diesel exhaust?
    Sixin S Lu
    College of Natural Resources, University of California, Berkeley, CA, USA
    Biomarkers 19:332-9. 2014
    ..DE exposures did not significantly alter urinary PAH levels. We conclude that urinary PAHs are not promising biomarkers of short-term exposures to DE in the range of 106-276 µg/m(3)...
  55. pmc Heritability and genomics of gene expression in peripheral blood
    Fred A Wright
    1 Bioinformatics Research Center, North Carolina State University, Raleigh, North Carolina, USA 2 Department of Statistics, North Carolina State University, Raleigh, North Carolina, USA 3 Department of Biological Sciences, North Carolina State University, Raleigh, North Carolina, USA 4
    Nat Genet 46:430-7. 2014
    ..Our results provide a new resource toward understanding the genetic control of transcription. ..
  56. pmc Molecular dosimetry of endogenous and exogenous O(6)-methyl-dG and N7-methyl-G adducts following low dose [D3]-methylnitrosourea exposures in cultured human cells
    Vyom Sharma
    Department of Environmental Sciences and Engineering, University of North Carolina, Campus Box 7431, Chapel Hill, North Carolina 27599 7431, United States
    Chem Res Toxicol 27:480-2. 2014
    ..The combined results do not support linear extrapolations to zero when data are available for science-based regulations...
  57. pmc Standardizing benchmark dose calculations to improve science-based decisions in human health assessments
    Jessica A Wignall
    Department of Environmental Sciences and Engineering, and
    Environ Health Perspect 122:499-505. 2014
    ....
  58. pmc Physiologically based pharmacokinetic (PBPK) modeling of interstrain variability in trichloroethylene metabolism in the mouse
    Weihsueh A Chiu
    National Center for Environmental Assessment, Office of Research and Development, U S Environmental Protection Agency, Washington, DC, USA
    Environ Health Perspect 122:456-63. 2014
    ..Traditionally, interindividual differences in the population are accounted for by default assumptions or, in rare cases, are based on human toxicokinetic data...
  59. pmc Toxic metal levels in children residing in a smelting craft village in Vietnam: a pilot biomonitoring study
    Alison P Sanders
    Department of Environmental Sciences and Engineering, Gillings School of Global Public Health, University of North Carolina Chapel Hill, Chapel Hill, North Carolina, USA
    BMC Public Health 14:114. 2014
    ..The aim of this study was to determine the body burden of toxic metals in children residing in a smelting craft village...
  60. pmc Integrative chemical-biological read-across approach for chemical hazard classification
    Yen Low
    Laboratory for Molecular Modeling, Division of Chemical Biology and Medicinal Chemistry, University of North Carolina, Chapel Hill, North Carolina 27599, USA
    Chem Res Toxicol 26:1199-208. 2013
    ..Identification of both chemical and biological features that give rise to the high accuracy of CBRA-based toxicity prediction facilitates mechanistic interpretation of the models. ..
  61. pmc Hydrocarbon-degrading bacteria enriched by the Deepwater Horizon oil spill identified by cultivation and DNA-SIP
    Tony Gutierrez
    1 Department of Environmental Sciences and Engineering, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC, USA 2 School of Life Sciences, Heriot Watt University, Edinburgh, UK
    ISME J 7:2091-104. 2013
    ....
  62. pmc Identification of putative estrogen receptor-mediated endocrine disrupting chemicals using QSAR- and structure-based virtual screening approaches
    Liying Zhang
    Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC, USA
    Toxicol Appl Pharmacol 272:67-76. 2013
    ....
  63. pmc Titanium dioxide nanoparticles activate the ATM-Chk2 DNA damage response in human dermal fibroblasts
    Raju Y Prasad
    Department of Environmental Sciences and Engineering, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC, USA
    Nanotoxicology 7:1111-9. 2013
    ..Taken together, these results demonstrate that exposure to nano-TiO2 activates the ATM/Chk2 DNA damage response pathway...
  64. pmc The aryl hydrocarbon receptor pathway: a key component of the microRNA-mediated AML signalisome
    Julia E Rager
    Department of Environmental Sciences and Engineering, Gillings School of Global Public Health, The University of North Carolina, 135 Dauer Drive, CB 7431, UNC, Chapel Hill, NC 27599, USA
    Int J Environ Res Public Health 9:1939-53. 2012
    ..These findings provide important insight into miRNA-regulated pathways in leukemia, and may help to prioritize targets for disease prevention and treatment...
  65. pmc Desorption of polycyclic aromatic hydrocarbons from field-contaminated soil to a two-dimensional hydrophobic surface before and after bioremediation
    Jing Hu
    Department of Environmental Sciences and Engineering, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC 27599 7431, USA
    Chemosphere 89:542-7. 2012
    ..The lower molecular weight PAHs had greater potential to desorb from soil than higher molecular weight PAHs. Biological treatment of the soil in a slurry-phase bioreactor completely eliminated PAH desorption to the C18 disks...
  66. pmc Leukemia-related chromosomal loss detected in hematopoietic progenitor cells of benzene-exposed workers
    L Zhang
    School of Public Health, Division of Environmental Health Sciences, University of California, Berkeley, CA, USA
    Leukemia 26:2494-8. 2012
    ....
  67. pmc Evaluating the effects of bioremediation on genotoxicity of polycyclic aromatic hydrocarbon-contaminated soil using genetically engineered, higher eukaryotic cell lines
    Jing Hu
    Department of Environmental Sciences and Engineering, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, North Carolina 27599 7431, United States
    Environ Sci Technol 46:4607-13. 2012
    ..Toxicity and genotoxicity bioassays can supplement chemical analysis-based risk assessment for contaminated soil when evaluating the efficacy of bioremediation...
  68. pmc Detection of PIGO-deficient cells using proaerolysin: a valuable tool to investigate mechanisms of mutagenesis in the DT40 cell system
    Jun Nakamura
    Department of Environmental Sciences and Engineering, University of North Carolina, Chapel Hill, North Carolina, United States of America
    PLoS ONE 7:e33563. 2012
    ..This novel assay for DT40 cells provides a valuable tool to investigate the mode of action of mutations caused by reactive agents using a series of isogenic mutant DT40 cells...
  69. pmc Heterologous expression of polycyclic aromatic hydrocarbon ring-hydroxylating dioxygenase genes from a novel pyrene-degrading betaproteobacterium
    David R Singleton
    Department of Environmental Sciences and Engineering, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, North Carolina, USA
    Appl Environ Microbiol 78:3552-9. 2012
    ..Only one of the six cloned RHDs was capable of transforming anthracene and benz[a]anthracene. None of the tested RHDs were capable of significantly transforming fluoranthene, chrysene, or benzo[a]pyrene...
  70. pmc O-hydroxylamine-coupled alkaline gel electrophoresis assay for the detection and measurement of DNA single-strand breaks
    April M Luke
    Department of Environmental Sciences and Engineering, University of North Carolina, Chapel Hill, NC, USA
    Methods Mol Biol 920:307-13. 2012
    ..Here, we describe a modified alkaline gel electrophoresis assay coupled with a neutral O-hydroxylamine to obtain the measurement of true SSB formation...
  71. pmc Polycyclovorans algicola gen. nov., sp. nov., an aromatic-hydrocarbon-degrading marine bacterium found associated with laboratory cultures of marine phytoplankton
    Tony Gutierrez
    Department of Environmental Sciences and Engineering, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, North Carolina, USA
    Appl Environ Microbiol 79:205-14. 2013
    ..Phytoplankton may be a natural biotope in the ocean where new species of hydrocarbon-degrading bacteria await discovery and which contribute significantly to natural remediation processes...
  72. pmc Formaldehyde carcinogenicity research: 30 years and counting for mode of action, epidemiology, and cancer risk assessment
    James A Swenberg
    Department of Environmental Sciences and Engineering, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, North Carolina 27599, USA
    Toxicol Pathol 41:181-9. 2013
    ....
  73. pmc Need for improved risk communication of fish consumption advisories to protect maternal and child health: influence of primary informants
    Catherine E Leprevost
    Department of Environmental and Molecular Toxicology, North Carolina State University, Box 7633, Raleigh, NC 27695, USA
    Int J Environ Res Public Health 10:1720-34. 2013
    ..g., women and children) for the creation of more targeted communications of fish consumption advisories...
  74. pmc Systems biology and birth defects prevention: blockade of the glucocorticoid receptor prevents arsenic-induced birth defects
    Bhavesh K Ahir
    Department of Environmental Sciences and Engineering, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA
    Environ Health Perspect 121:332-8. 2013
    ..Systems biology-based approaches may help to identify key pathways that mediate metal-induced birth defects as well as potential targets for prevention...
  75. pmc Empirical pathway analysis, without permutation
    Yi Hui Zhou
    Department of Biostatistics, University of North Carolina, Chapel Hill, NC 27599, USA
    Biostatistics 14:573-85. 2013
    ..Extensions for inclusion of covariates and censored data are described, and we test the performance of our procedures using simulations based on real datasets. These approaches have been implemented in the new R package safeExpress...
  76. pmc Biomarkers of exposure and effect in human lymphoblastoid TK6 cells following [13C2]-acetaldehyde exposure
    Benjamin C Moeller
    Curriculum in Toxicology, University of North Carolina, Chapel Hill, North Carolina 27599, USA
    Toxicol Sci 133:1-12. 2013
    ..These data can replace default assumptions of linear extrapolation to very low doses of exogenous acetaldehyde for risk prediction...
  77. pmc Formaldehyde and epigenetic alterations: microRNA changes in the nasal epithelium of nonhuman primates
    Julia E Rager
    Department of Environmental Sciences and Engineering, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA
    Environ Health Perspect 121:339-44. 2013
    ..Our previous investigation demonstrated that formaldehyde exposure in human lung cells caused disruptions in miRNA expression profiles in vitro...
  78. pmc Molecular mechanisms of fibrosis-associated promotion of liver carcinogenesis
    Takeki Uehara
    Department of Environmental Sciences and Engineering, University of North Carolina, Chapel Hill, NC, USA
    Toxicol Sci 132:53-63. 2013
    ..These results may contribute to identification of cirrhotic patients predisposed to HCC by analyzing the expression of hepatic progenitor cell markers in the noncancerous liver tissue...
  79. pmc Acetaminophen-induced acute liver injury in HCV transgenic mice
    Takeki Uehara
    Department of Environmental Sciences and Engineering, University of North Carolina, Chapel Hill, NC 27599, USA
    Toxicol Appl Pharmacol 266:224-32. 2013
    ..In fed mice dosed with 300 mg/kg acetaminophen, we observed that liver mitochondria in HCV-Tg mice exhibited signs of dysfunction showing the potential mechanism for increased susceptibility...
  80. pmc Single-nucleotide polymorphisms associated with skin naphthyl-keratin adduct levels in workers exposed to naphthalene
    Rong Jiang
    Department of Environmental Sciences and Engineering, Gillings School of Global Public Health, University of North Carolina Chapel Hill, Chapel Hill, North Carolina 27599 7431, USA
    Environ Health Perspect 120:857-64. 2012
    ..Individual genetic variation that results in differences in systemic response to xenobiotic exposure is not accounted for as a predictor of outcome in current exposure assessment models...
  81. pmc Abasic sites preferentially form at regions undergoing DNA replication
    Paul D Chastain
    Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599 7525, USA
    FASEB J 24:3674-80. 2010
    ..They also reveal that there is increased susceptibility to oxidative damage in DNA regions undergoing replication, which may explain the previously observed clustering of AP sites...
  82. ncbi Quantifying the relative importance of predictors in multiple linear regression analyses for public health studies
    Yi Chun E Chao
    Department of Environmental Sciences and Engineering, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599 7431, USA
    J Occup Environ Hyg 5:519-29. 2008
    ..Johnson's Relative Weight involves significantly less computational burden than the General Dominance Index when the number of predictors in the final model is large...
  83. ncbi Cells deficient in the FANC/BRCA pathway are hypersensitive to plasma levels of formaldehyde
    John R Ridpath
    Department of Environmental Sciences and Engineering, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA
    Cancer Res 67:11117-22. 2007
    ....
  84. ncbi Effects of enrichment with phthalate on polycyclic aromatic hydrocarbon biodegradation in contaminated soil
    David R Singleton
    Department of Environmental Sciences and Engineering, School of Public Health, University of North Carolina, Chapel Hill, NC 27599, USA
    Biodegradation 19:577-87. 2008
    ....
  85. pmc Time course investigation of PPARalpha- and Kupffer cell-dependent effects of WY-14,643 in mouse liver using microarray gene expression
    Courtney G Woods
    Department of Environmental Sciences and Engineering, University of North Carolina, Chapel Hill, NC 27599 7431, USA
    Toxicol Appl Pharmacol 225:267-77. 2007
    ..To the contrary, a strong PPARalpha-specific gene signature was evident in mice that were continually exposed to WY-14,643...
  86. ncbi Sensory irritation response in rats: modeling, analysis and validation
    Karen A Yokley
    Center for Research in Scientific Computation and Department of Mathematics, North Carolina State University, Raleigh, NC, USA
    Bull Math Biol 70:555-88. 2008
    ..The model predicts the formaldehyde data well, and hence the model is thought to be a reasonable description of the physiological system of sensory irritation. The model is also expected to translate well to other irritants...
  87. ncbi Genetic polymorphisms and benzene metabolism in humans exposed to a wide range of air concentrations
    Sungkyoon Kim
    School of Public Health, University of North Carolina, Chapel Hill, NC 27599, USA
    Pharmacogenet Genomics 17:789-801. 2007
    ....
  88. ncbi Impacts of microbial redox conditions on the phase distribution of pyrene in soil-water systems
    Han S Kim
    Environmental Engineering, Konkuk University, 1 Hwayang dong, Gwangjin gu, Seoul 143 701, Korea
    Environ Pollut 152:106-15. 2008
    ..Our results suggest that the microbially mediated redox conditions have significant impacts on SOM and should be considered for the transport, fate, bioavailability, and exposure risk of HOCs in the geo-environments...
  89. pmc PBTK modeling demonstrates contribution of dermal and inhalation exposure components to end-exhaled breath concentrations of naphthalene
    David Kim
    Department of Environmental Sciences and Engineering, School of Public Health, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599 7431, USA
    Environ Health Perspect 115:894-901. 2007
    ..However, a quantitative understanding of the relationship between external exposures and end-exhaled air concentrations has not been described for occupational and environmental exposure scenarios...
  90. pmc Albumin adducts of electrophilic benzene metabolites in benzene-exposed and control workers
    Yu Sheng Lin
    Department of Environmental Sciences and Engineering, School of Public Health, University of North Carolina, Chapel Hill, North Carolina 27599 7431, USA
    Environ Health Perspect 115:28-34. 2007
    ..Metabolism of benzene produces reactive electrophiles, including benzene oxide (BO), 1,4-benzoquinone (1,4-BQ), and 1,2-benzoquinone (1,2-BQ), that are capable of reacting with blood proteins to produce adducts...
  91. ncbi Modeling the removal of dissolved organic carbon by ion exchange in a completely mixed flow reactor
    Treavor H Boyer
    Department of Environmental Sciences and Engineering, School of Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599 7431, USA
    Water Res 42:1897-906. 2008
    ..The model was validated using continuous-flow data from two pilot plant studies. Model predictions were found to be in good agreement with the observed pilot plant data...
  92. ncbi Biomarkers in toxicology and risk assessment: informing critical dose-response relationships
    James A Swenberg
    Department of Environmental Sciences and Engineering, University of North Carolina, Chapel Hill, North Carolina 27599, USA
    Chem Res Toxicol 21:253-65. 2008
    ..It is also clear, however, that low dose data on mutagenesis are needed for many more chemicals...
  93. ncbi Effect of incubation conditions on the enrichment of pyrene-degrading bacteria identified by stable-isotope probing in an aged, PAH-contaminated soil
    Maiysha D Jones
    Department of Environmental Sciences and Engineering, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599 7431, USA
    Microb Ecol 56:341-9. 2008
    ..Of the four sequences from slurry incubations not within this clade, three possessed greater than 99% similarity to the 16S rRNA gene sequences of phylogenetically dissimilar Caulobacter spp...
  94. pmc Accumulation of M1dG DNA adducts after chronic exposure to PCBs, but not from acute exposure to polychlorinated aromatic hydrocarbons
    Yo Chan Jeong
    Department of Environmental Sciences and Engineering, University of North Carolina at Chapel Hill, NC 27599, USA
    Free Radic Biol Med 45:585-91. 2008
    ..In summary, the results from the present study support the hypothesis that oxidative DNA damage plays a key role in toxicity and carcinogenicity following long-term PCB exposure...

Research Grants30

  1. 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. ..