This project is designed to improve our understanding of the genotoxic effects of complex mixtures. Because of the large number of complex mixtures to which the public is exposed, the research will be of value to bother health professionals and the regulatory community. The research will focus on mixtures of polycyclic aromatic hydrocarbons (PAHs), such as coal tar or petroleum waste; and mixtures of PAHs and halogenated aromatic hydrocarbons (HAHs), such as wood preserving waste. Samples to be evaluated will include complex mixtures, isolated fractions, model compounds, and reconstituted mixtures. These samples will be evaluated using a tier system. The first tier will employ microbial genotoxicity assays to characterize the potential of a sample to induce point mutations, and gap junctional intercellular communication to measure the epigenetic potential of a sample. Tier two will measure the formation of DNA adducts in vivo as well as gene expression (primarily metabolic enzymes) as affected by exposure to complex mixtures. In addition, studies will be conducted to measure expression of p53, p21, or Gadd45 proteins following exposure to mixtures or model chemicals. These initial studies will be used to identify proteins following exposure to mixtures of model chemicals. These initial studies will be used to identify factors governing the metabolism of mixtures, as well as the initiation, promotion and progression of malignant cells. From these studies, two complex mixtures (and appropriate model compounds and reconstituted fractions) will be selected for investigation in a long-term rodent study. Two sensitive models will be employed based on the results of tiers one and two. The purpose of the third tier will be to determine if the effects and interactions observed in tier one and two testing are replicated in an animal model; and, do these effects have relevance to human cancer.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Hazardous Substances Basic Research Grants Program (NIEHS) (P42)
Project #
5P42ES004917-13
Application #
6442527
Study Section
Special Emphasis Panel (ZES1)
Project Start
2001-04-01
Project End
2002-03-31
Budget Start
Budget End
Support Year
13
Fiscal Year
2001
Total Cost
$73,465
Indirect Cost
Name
Texas A&M University
Department
Type
DUNS #
047006379
City
College Station
State
TX
Country
United States
Zip Code
77845
Phillips, Tracie D; Richardson, Molly; Cheng, Yi-Shing Lisa et al. (2015) Mechanistic relationships between hepatic genotoxicity and carcinogenicity in male B6C3F1 mice treated with polycyclic aromatic hydrocarbon mixtures. Arch Toxicol 89:967-77
Barhoumi, Rola; Mouneimne, Youssef; Chapkin, Robert S et al. (2014) Effects of fatty acids on benzo[a]pyrene uptake and metabolism in human lung adenocarcinoma A549 cells. PLoS One 9:e90908
dela Cruz, Albert Leo N; Cook, Robert L; Dellinger, Barry et al. (2014) Assessment of environmentally persistent free radicals in soils and sediments from three Superfund sites. Environ Sci Process Impacts 16:44-52
Wlodarczyk, Bogdan J; Zhu, Huiping; Finnell, Richard H (2014) Mthfr gene ablation enhances susceptibility to arsenic prenatal toxicity. Toxicol Appl Pharmacol 275:22-7
Taylor, John F; Robinson, Abraham; Mitchell, Nicole J et al. (2013) In vivo efficacy of ferrihydrite as an enterosorbent for arsenic: short-term evaluation in rodents. J Toxicol Environ Health A 76:167-75
Dash, Bhagirathi; Phillips, Timothy D (2012) Molecular characterization of a catalase from Hydra vulgaris. Gene 501:144-52
Theodorakis, Christopher W; Bickham, John W; Donnelly, Kirby C et al. (2012) DNA damage in cichlids from an oil production facility in Guatemala. Ecotoxicology 21:496-511
Barhoumi, Rola; Mouneimne, Youssef; Ramos, Ernesto et al. (2011) Multiphoton spectral analysis of benzo[a]pyrene uptake and metabolism in a rat liver cell line. Toxicol Appl Pharmacol 253:45-56
Kelley, Matthew A; Gillespie, Annika; Zhou, Guo-Dong et al. (2011) In situ biomonitoring of caged, juvenile Chinook salmon (Oncorhynchus tshawytscha) in the Lower Duwamish Waterway. Mar Pollut Bull 62:2520-32
Rinner, Brian P; Matson, Cole W; Islamzadeh, Arif et al. (2011) Evolutionary toxicology: contaminant-induced genetic mutations in mosquitofish from Sumgayit, Azerbaijan. Ecotoxicology 20:365-76

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