Polycyclic aromatic hydrocarbons (PAHs) are a family of toxicants that are ubiquitous in the environment. These contaminants generate considerable interest, because some of them are highly carcinogenic in laboratory animals and have been implicated in breast, lung, and colon cancers in humans. These chemicals commonly enter the human body through inhalation of cigarette smoke or consumption of contaminated food. Of these two pathways, dietary intake of PAHs constitutes a major source of exposure in humans. Although many reviews and books on PAHs have been published, factors affecting the accumulation of PAHs in the diet, their absorption following ingestion, and strategies to assess risk from exposure to these hydrocarbons following ingestion have received much less attention. This review, therefore, focuses on concentrations of PAHs in widely consumed dietary ingredients along with gastrointestinal absorption rates in humans. Metabolism and bioavailability of PAHs in animal models and the processes, which influence the disposition of these chemicals, are discussed. The utilitarian value of structure and metabolism in predicting PAH toxicity and carcinogenesis is also emphasized. Finally, based on intake, disposition, and tumorigenesis data, the exposure risk to PAHs from diet, and contaminated soil is presented. This information is expected to provide a framework for refinements in risk assessment of PAHs from a multimedia exposure perspective.

The lack of progress in reducing health disparities suggests that new approaches are needed if we are to achieve meaningful, equitable, and lasting reductions. Current scientific paradigms do not adequately capture the complexity of the relationships between environment, personal health and population level disparities. The public health exposome is presented as a universal exposure tracking framework for integrating complex relationships between exogenous and endogenous exposures across the lifespan from conception to death. It uses a social-ecological framework that builds on the exposome paradigm for conceptualizing how exogenous exposures “get under the skin”. The public health exposome approach has led our team to develop a taxonomy and bioinformatics infrastructure to integrate health outcomes data with thousands of sources of exogenous exposure, organized in four broad domains: natural, built, social, and policy environments. With the input of a transdisciplinary team, we have borrowed and applied the methods, tools and terms from various disciplines to measure the effects of environmental exposures on personal and population health outcomes and disparities, many of which may not manifest until many years later. As is customary with a paradigm shift, this approach has far reaching implications for research methods and design, analytics, community engagement strategies, and research training.

To test whether the presence of charged residues at position P14 of the reactive center region of noninhibitory members of the serpin family of protein proteinase inhibitors is responsible for their lack of proteinase inhibitory properties, we expressed a variant of the alpha 1-proteinase inhibitor (alpha 1-PI) with arginine substituted for threonine at this position (T345R) and characterized its functional properties. Although the T345R variant reacted with proteinases principally as a substrate, it was still capable of forming stable complexes with the three serine proteinases examined, human neutrophil elastase (HNE), porcine pancreatic elastase (PPE), and trypsin. The fraction of T345R alpha 1-PI that formed a complex with proteinase was quantitated by autoradiography of SDS gels of the variant incubated with 125I-labeled proteinase. The stoichiometry of inhibition (S.I.) (number of mol of alpha 1-PI required to completely inhibit 1 mol of proteinase), which was 1 for both plasma alpha 1-PI and wild-type recombinant alpha 1-PI interacting with each of the proteinases, was very much greater than 1 for T345R variant alpha 1-PI. Values of 9.5, 45, and about 70 were estimated for variant alpha 1-PI inhibition of trypsin, HNE, and PPE, respectively. An inverse relationship between the apparent second-order rate constant and the S.I. for inhibition of PPE by T345R alpha 1-PI suggested that the mutation did not affect the rate-determining step of formation of a transient intermediate complex. Following cleavage of the reactive center loop, there was a large increase in protein stability and changes in the CD spectrum, both consistent with insertion of the reactive center loop into beta-sheet A. This behavior is similar to that of wild-type alpha 1-PI. We conclude that the presence of a charged residue at P14 does not prevent reactive center loop insertion or the functioning of alpha 1-PI as an inhibitor of serine proteinases but does significantly alter the relative rates of the substrate and inhibitory pathways in favor of the former, probably by reducing the rate of the latter reaction.

The focus of this study was to characterize the impact of gestational exposure to benzo(a)pyrene, [B (a)P] on modulation of glutamate receptor subunit expression that is critical for the maintenance of synaptic plasticity mechanisms during hippocampal or cortical development in offspring. Previous studies have demonstrated that hippocampal and/or cortical synaptic plasticity (as measured by longterm potentiation and S1-cortex spontaneous/evoked neuronal activity) and learning behavior (as measured by fixed-ratio performance operant testing) is significantly impaired in polycyclic aromatic or halogenated aromatic hydrocarbon-exposed offspring as compared to controls. These previous studies have also revealed that brain to body weight ratios are greater in exposed offspring relative to controls indicative of intrauterine growth retardation which has been shown to manifest as low birth weight in offspring. Recent epidemiological studies have identified an effect of prenatal exposure to airborne polycyclic aromatic hydrocarbons on neurodevelopment in the first 3 Years of life among inner-city children (Perera et al., 2006). The present study utilizes a well-characterized animal model to test the hypothesis that gestational exposure to B(a)P causes dysregulation of developmental ionotropic glutamate receptor subunit expression, namely the N-methyl-D-aspartate receptor (NMDAR) and α-amino-3-hydroxy-5-methyl-4-isoxazole-propionate receptor (AMPAR) both critical to the expression of synaptic plasticity mechanisms. To mechanistically ascertain the basis of B(a)P-induced plasticity perturbations, timed pregnant Long-Evans rats were exposed in an oral subacute exposure regimen to 0, 25 and 150µg/kg BW B(a)P on gestation days 14-17. The first sub-hypothesis tested whether gestational exposure to B(a)P would result in significant disposition in offspring. The second sub-hypothesis tested whether gestational exposure to B(a)P would result in downregulation of early developmental expression of NMDA and AMPA receptor subunits in the *Corresponding author: Darryl B. Hood, Ph.D., Department of Neurobiology and Neurotoxicology, Center for Molecular and Behavioral Neuroscience, Meharry Medical College, Nashville, TN 37208, USA. Phone (615) 327-6358, FAX: (615) 327-6632. email: dhood@mmc.edu. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. hippocampus of offspring as well as in primary neuronal cultures. The results of these studies revealed significant: 1) disposition to the hippocampus and cortex, 2) down-regulation of developmental glutamate receptor mRNA and protein subunit expres...

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