Polycyclic Aromatic Hydrocarbons (PAHs) are a re-emerging class of environmental pollutants formed from incomplete combustion of fossil fuels (diesel or gasoline exhaust, burning of coal, petroleum or tobacco) and found at Superfund sites. Increasing energy needs world-wide, especially in countries such as China, are the reason why PAHs, unlike other Superfund contaminants of concern in the past (e.g., PCBs, TCDD, etc.), will be increasing over the next quarter century. PAHs produce cancers at multiple sites in animal models and, in fact, were the first class of chemicals identified as environmental carcinogens. Even so, we know relatively little about critical aspects of PAH-dependent carcinogenesis. Much of the work to date has, for simplicity, employed a single PAH, such as benzo[a]pyrene (BaP) or dibenzo[a,l]pyrene (DBP) rather than actual environmental mixtures. In this proposal we compare the carcinogenicity of PAH mixtures, from locations where high human exposures are known or suspected, to BaP and DBP in two cancer models. The first, skin cancer, is rapidly increasing in incidence world-wide. The second model is novel and innovative and examines transplacental lymphorna (significant cancer in children), lung (highest mortality in U.S.) and liver (highest mortality in parts of the world and increasing in the U.S.) In studying these environmentally relevant PAH mixtures, we address critical questions of mechanism and the potential for intervention by chemoprevention. The common mechanistic goals in both cancer models provide a high degree of integration. The human relevance has been markedly enhanced with the use of the """"""""Humanized"""""""" CYP1B1 mouse studies and the connection to project 2 strengthened by our use of accelerator mass spectrometry to examine DBP pharmacokinetics in human volunteers, an unprecendented approach. Preliminary studies have already demonstrated the success of this approach with aflatoxin B1 in humans and the effect of coadministration with the chemopreventive agent, chlorophyllin. Thus, this project, focusing on PAH-dependent carcinogenesis, is highly relevant to human health concerns associated with Superfund sites. In addition, it complements very well the endpoints pursued by the other biomedical research projects and makes excellent use of the resources and materials provided by the Cores. Finally, our creative use of new technologies has markedly increased the translational nature of the research.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Hazardous Substances Basic Research Grants Program (NIEHS) (P42)
Project #
5P42ES016465-02
Application #
8056112
Study Section
Special Emphasis Panel (ZES1)
Project Start
Project End
Budget Start
2010-04-01
Budget End
2011-03-31
Support Year
2
Fiscal Year
2010
Total Cost
$329,560
Indirect Cost
Name
Oregon State University
Department
Type
DUNS #
053599908
City
Corvallis
State
OR
Country
United States
Zip Code
97339
Haggard, Derik E; Noyes, Pamela D; Waters, Katrina M et al. (2018) Transcriptomic and phenotypic profiling in developing zebrafish exposed to thyroid hormone receptor agonists. Reprod Toxicol 77:80-93
Hummel, Jessica M; Madeen, Erin P; Siddens, Lisbeth K et al. (2018) Pharmacokinetics of [14C]-Benzo[a]pyrene (BaP) in humans: Impact of Co-Administration of smoked salmon and BaP dietary restriction. Food Chem Toxicol 115:136-147
Balik-Meisner, Michele; Truong, Lisa; Scholl, Elizabeth H et al. (2018) Population genetic diversity in zebrafish lines. Mamm Genome 29:90-100
Balik-Meisner, Michele; Truong, Lisa; Scholl, Elizabeth H et al. (2018) Elucidating Gene-by-Environment Interactions Associated with Differential Susceptibility to Chemical Exposure. Environ Health Perspect 126:067010
Geier, Mitra C; James Minick, D; Truong, Lisa et al. (2018) Systematic developmental neurotoxicity assessment of a representative PAH Superfund mixture using zebrafish. Toxicol Appl Pharmacol 354:115-125
Tan, Yu-Mei; Leonard, Jeremy A; Edwards, Stephen et al. (2018) Aggregate Exposure Pathways in Support of Risk Assessment. Curr Opin Toxicol 9:8-13
Titaley, Ivan A; Ogba, O Maduka; Chibwe, Leah et al. (2018) Automating data analysis for two-dimensional gas chromatography/time-of-flight mass spectrometry non-targeted analysis of comparative samples. J Chromatogr A 1541:57-62
Geier, Mitra C; Chlebowski, Anna C; Truong, Lisa et al. (2018) Comparative developmental toxicity of a comprehensive suite of polycyclic aromatic hydrocarbons. Arch Toxicol 92:571-586
Bugel, Sean M; Tanguay, Robert L (2018) Multidimensional chemobehavior analysis of flavonoids and neuroactive compounds in zebrafish. Toxicol Appl Pharmacol 344:23-34
Garcia, Gloria R; Bugel, Sean M; Truong, Lisa et al. (2018) AHR2 required for normal behavioral responses and proper development of the skeletal and reproductive systems in zebrafish. PLoS One 13:e0193484

Showing the most recent 10 out of 174 publications