Abstract

This project proposes to conduct several interrelated studies with individual polycyclic aromatic hydrocarbons (PAHs) and reconstituted PAH mixtures to determine the interactions of these compounds and the role of these interactions in PAH-induced carcinogenicity. The classes of PAH compounds to be studied include the polychlorinated biphenyls (PCBs), polychlorinated dibenzo-p-dioxins (PCDDs) and the polychlorinated dibenzofurans (PCDFs). The proposed studies include: (1) analysis of the comparative induction of CYP1A1 and CYP1A2 gene expression by a reconstituted PAH mixture and the 2-,3- and > 4-ring PAH fractions to determine the relative contributions of the different fractions to the overall induction potency of the mixture; (2) extension of (1) to include other Ah receptor-mediated responses; (3) investigation of the selective induction of CYP1A2 by acenaphthylene with regard to its toxicologic and carcinogenic significance; and (4) investigation of the interactions of strong carcinogens that are poor microsomal P450 enzyme inducers and weak carcinogens that are potent microsomal P450 enzyme inducers. The results obtained will determine the extent of the non-additive interactions between PCBs and PCDDs/PCDFs and provide critical data which can be used to evaluate the utility of the TEF model for risk assessment of HAHs.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Hazardous Substances Basic Research Grants Program (NIEHS) (P42)
Project #
5P42ES004917-10
Application #
6271112
Study Section
Project Start
1998-04-01
Project End
1999-03-31
Budget Start
1997-10-01
Budget End
1998-09-30
Support Year
10
Fiscal Year
1998
Total Cost
Indirect Cost

  Institution

Name
Texas A&M University
Department
Type
DUNS #
047006379
City
College Station
State
TX
Country
United States
Zip Code
77845

  Publications

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
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
Dash, Bhagirathi; Phillips, Timothy D (2012) Molecular characterization of a catalase from Hydra vulgaris. Gene 501:144-52
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

Showing the most recent 10 out of 268 publications