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 co-administration 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.

National Institute of Health (NIH)
National Institute of Environmental Health Sciences (NIEHS)
Hazardous Substances Basic Research Grants Program (NIEHS) (P42)
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Oregon State University
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Garcia, Gloria R; Goodale, Britton C; Wiley, Michelle W et al. (2017) In Vivo Characterization of an AHR-Dependent Long Noncoding RNA Required for Proper Sox9b Expression. Mol Pharmacol 91:609-619
Donald, Carey E; Anderson, Kim A (2017) Assessing soil-air partitioning of PAHs and PCBs with a new fugacity passive sampler. Sci Total Environ 596-597:293-302
Wittwehr, Clemens; Aladjov, Hristo; Ankley, Gerald et al. (2017) How Adverse Outcome Pathways Can Aid the Development and Use of Computational Prediction Models for Regulatory Toxicology. Toxicol Sci 155:326-336
Madeen, Erin P; Williams, David E (2017) Environmental PAH exposure and male idiopathic infertility: a review on early life exposures and adult diagnosis. Rev Environ Health 32:73-81
Shrivastava, Manish; Lou, Silja; Zelenyuk, Alla et al. (2017) Global long-range transport and lung cancer risk from polycyclic aromatic hydrocarbons shielded by coatings of organic aerosol. Proc Natl Acad Sci U S A 114:1246-1251
Geier, Mitra C; Chlebowski, Anna C; Truong, Lisa et al. (2017) Comparative developmental toxicity of a comprehensive suite of polycyclic aromatic hydrocarbons. Arch Toxicol :
Knecht, Andrea L; Truong, Lisa; Simonich, Michael T et al. (2017) Developmental benzo[a]pyrene (B[a]P) exposure impacts larval behavior and impairs adult learning in zebrafish. Neurotoxicol Teratol 59:27-34
Zhang, Guozhu; Truong, Lisa; Tanguay, Robert L et al. (2017) A New Statistical Approach to Characterize Chemical-Elicited Behavioral Effects in High-Throughput Studies Using Zebrafish. PLoS One 12:e0169408
Madeen, Erin P; Löhr, Christiane V; You, Hannah et al. (2017) Dibenzo[def,p]chrysene transplacental carcinogenesis in wild-type, Cyp1b1 knockout, and CYP1B1 humanized mice. Mol Carcinog 56:163-171
Knecht, Andrea L; Truong, Lisa; Marvel, Skylar W et al. (2017) Transgenerational inheritance of neurobehavioral and physiological deficits from developmental exposure to benzo[a]pyrene in zebrafish. Toxicol Appl Pharmacol 329:148-157

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