This application entitled Genetic/Epigenetic Susceptibility to Superfund Chemicals utilizes the disciplines of biomedicine, molecular biology, ecology, and engineering to assess the potential hazardous impact of toxic metals on humans and upon aquatic ecosystems. An underlying theme involves factors responsible for differences in genetic susceptibility of human responses to carcinogenic and toxic metals. The ecology and engineering projects will study how to reduce human exposure to these same Superfund toxic metals. The focus of the research for most project is on arsenic, chromium, and nickel and their interactions with toxic organics, such as PAH's. There are 4 biomedical projects: 1) Epigenetic Effects on Individual Susceptibility to Heavy Metal and Polycyclic Aromatic Hydrocarbon-induced DNA damage (E. Tang); 2) Detection of Cr-DNA Adducts in Human Cells (M. Costa); 3) Metal-induced Inflammatory Factors, Oxidative Stress, and Suppression of Their Effects (K. Frenkel); 4) Identification and Genetic Analysis of the Human Arsenic Efflux Pump (T. Rossman). There are 3 non-biomedical projects: 1) Mechanisms of Resistance of Aquatic Vertebrate Populations to Mixtures of Aromatic Hydrocarbon and Metal Contaminants (I. Wirgin); 2) Microbial Biogeochemical Cycling of Arsenic and of Chromium Coupled to the Biodegradation of Aromatic Contaminant Compounds (L. Young); 3) Water-Sediment Model and Criteria for Arsenic and Chrome (D.Di Toro). There is one Molecular Biology Research Support Core which supports the biomedical projects by providing expertise in utilizing the UvrABC excision method in combination with ligation-medicated PCR to map sites of metal and polycyclic aromatic hydrocarbon-induced DNA adducts. The Molecular Biology Core also supports the Affymetrix GeneChip technology and other molecular biology instruments. This program project is directed by an Administrative Core which will be responsible for planning and coordination. The Administrative Core supports a unique Government Liaison unit which reaches out to local EPA Region 2 scientific personnel. With the involvement of the EPA, Outreach specialist, molecular biologists, biomedical scientists, and engineers, we have created a truly multi-disciplinary program.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Hazardous Substances Basic Research Grants Program (NIEHS) (P42)
Project #
5P42ES010344-04
Application #
6635505
Study Section
Special Emphasis Panel (ZES1-MAO-A (G2))
Program Officer
Thompson, Claudia L
Project Start
2000-06-01
Project End
2005-03-31
Budget Start
2003-06-05
Budget End
2004-03-31
Support Year
4
Fiscal Year
2003
Total Cost
$2,161,685
Indirect Cost
Name
New York University
Department
Public Health & Prev Medicine
Type
Schools of Medicine
DUNS #
121911077
City
New York
State
NY
Country
United States
Zip Code
10016
Brocato, Jason; Hernandez, Michelle; Laulicht, Freda et al. (2015) In Vivo Exposures to Particulate Matter Collected from Saudi Arabia or Nickel Chloride Display Similar Dysregulation of Metabolic Syndrome Genes. J Toxicol Environ Health A 78:1421-36
Brocato, Jason; Chen, Danqi; Liu, Jianli et al. (2015) A Potential New Mechanism of Arsenic Carcinogenesis: Depletion of Stem-Loop Binding Protein and Increase in Polyadenylated Canonical Histone H3.1 mRNA. Biol Trace Elem Res 166:72-81
Brocato, Jason; Costa, Max (2015) SATB1 and 2 in colorectal cancer. Carcinogenesis 36:186-91
Brocato, Jason; Wu, Fen; Chen, Yu et al. (2015) Association between sleeping hours and cardiometabolic risk factors for metabolic syndrome in a Saudi Arabian population. BMJ Open 5:e008590
Niu, Yingmei; DesMarais, Thomas L; Tong, Zhaohui et al. (2015) Oxidative stress alters global histone modification and DNA methylation. Free Radic Biol Med 82:22-8
Brocato, Jason; Chervona, Yana; Costa, Max (2014) Molecular responses to hypoxia-inducible factor 1? and beyond. Mol Pharmacol 85:651-7
Brocato, Jason; Fang, Lei; Chervona, Yana et al. (2014) Arsenic induces polyadenylation of canonical histone mRNA by down-regulating stem-loop-binding protein gene expression. J Biol Chem 289:31751-64
Brocato, Jason; Costa, Max (2013) Basic mechanics of DNA methylation and the unique landscape of the DNA methylome in metal-induced carcinogenesis. Crit Rev Toxicol 43:493-514
Arita, Adriana; Muñoz, Alexandra; Chervona, Yana et al. (2013) Gene expression profiles in peripheral blood mononuclear cells of Chinese nickel refinery workers with high exposures to nickel and control subjects. Cancer Epidemiol Biomarkers Prev 22:261-9
Passantino, Lisa; Muñoz, Alexandra B; Costa, Max (2013) Sodium metavanadate exhibits carcinogenic tendencies in vitro in immortalized human bronchial epithelial cells. Metallomics 5:1357-67

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