Evaluation of polycyclic aromatic hydrocarbons using analytical methods, toxicology, and risk assessment research: seafood safety after a petroleum spill as an example.

BackgroundPolycyclic aromatic hydrocarbons (PAHs) are abundant and widespread environmental chemicals. They are produced naturally and through man-made processes, and they are common in organic media, including petroleum. Several PAHs are toxic, and a subset exhibit carcinogenic activity. PAHs represent a range of chemical structures based on two or more benzene rings and, depending on their source, can exhibit a variety of side modifications resulting from oxygenation, nitrogenation, and alkylation.ObjectivesHere we discuss the increasing ability of contemporary analytical methods to distinguish not only different chemical structures among PAHs but also their concentrations in environmental media. Using seafood contamination following the Deepwater Horizon accident as an example, we identify issues that are emerging in the PAH risk assessment process because of increasing analytical sensitivity for individual PAHs, and we describe the paucity of toxicological literature for many of these compounds.DiscussionPAHs, including the large variety of chemically modified or substituted PAHs, are naturally occurring and may constitute health risks if human populations are exposed to hazardous levels. However, toxicity evaluations have not kept pace with modern analytic methods and their increased ability to detect substituted PAHs. Therefore, although it is possible to measure these compounds in seafood and other media, we do not have sufficient information on the potential toxicity of these compounds to incorporate them into human health risk assessments and characterizations.ConclusionsFuture research efforts should strategically attempt to fill this toxicological knowledge gap so human health risk assessments of PAHs in environmental media or food can be better determined. This is especially important in the aftermath of petroleum spills

Persistence and Repair of Bifunctional DNA Adducts in Tissues of Laboratory Animals Exposed to 1,3-Butadiene by Inhalation

1,3-butadiene (BD) is an important industrial and environmental chemical classified as a human carcinogen. The mechanism of BD-mediated cancer is of significant interest because of the widespread exposure of humans to BD from cigarette smoke and urban air. BD is metabolically activated to 1,2,3,4-diepoxybutane (DEB), which is a highly genotoxic and mutagenic bis-alkylating agent believed to be the ultimate carcinogenic species of BD. We have previously identified several types of DEB-specific DNA adducts, including bis-N7-guanine cross-links (bis-N7-BD), N6-adenine-N7-guanine cross-links (N6A-N7G-BD), and 1,N6-dA exocyclic adducts. These lesions were detected in tissues of laboratory rodents exposed to BD by inhalation (Goggin et al. Cancer Res. 2009;69:2479–2486). In the present work, persistence and repair of bifunctional DEB-DNA adducts in tissues of mice and rats exposed to BD by inhalation were investigated. The half-lives of the most abundant cross-links, bis-N7G-BD, in mouse liver, kidney, and lungs were 2.3–2.4 days, 4.6–5.7 days, and 4.9 days, respectively. The in vitro half-lives of bis-N7G-BD were 3.5 days (S,S isomer) and 4.0 days (meso isomer) due to their spontaneous depurination. In contrast, tissue concentrations of the minor DEB adducts, N7G-N1A-BD and 1,N6-HMHP-dA, remained essentially unchanged during the course of the experiment, with an estimated t 1/2 of 36–42 days. No differences were observed between DEB-DNA adduct levels in BD-treated wild type mice and the corresponding animals deficient in methyl purine glycosylase or the Xpa gene. Our results indicate that DEB-induced N7G-N1A-BD and 1,N6-HMHP-dA adducts persist in vivo, potentially contributing to mutations and cancer observed as a result of BD exposure

Elevated mitochondrial genome variation after 50 generations of radiation exposure in a wild rodent

Currently, the effects of chronic, continuous low dose environmental irradiation on the mitochondrial genome of resident small mammals are unknown. Using the bank vole (Myodes glareolus) as a model system, we tested the hypothesis that approximately 50 generations of exposure to the Chernobyl environment has significantly altered genetic diversity of the mitochondrial genome. Using deep sequencing, we compared mitochondrial genomes from 131 individuals from reference sites with radioactive contamination comparable to that present in northern Ukraine before the 26 April 1986 meltdown, to populations where substantial fallout was deposited following the nuclear accident. Population genetic variables revealed significant differences among populations from contaminated and uncontaminated localities. Therefore, we rejected the null hypothesis of no significant genetic effect from 50 generations of exposure to the environment created by the Chernobyl meltdown. Samples from contaminated localities exhibited significantly higher numbers of haplotypes and polymorphic loci, elevated genetic diversity, and a significantly higher average number of substitutions per site across mitochondrial gene regions. Observed genetic variation was dominated by synonymous mutations, which may indicate a history of purify selection against nonsynonymous or insertion/deletion mutations. These significant differences were not attributable to sample size artifacts. The observed increase in mitochondrial genomic diversity in voles from radioactive sites is consistent with the possibility that chronic, continuous irradiation resulting from the Chernobyl disaster has produced an accelerated mutation rate in this species over the last 25 years. Our results, being the first to demonstrate this phenomenon in a wild mammalian species, are important for understanding genetic consequences of exposure to low-dose radiation sources. © 2017 John Wiley & Sons Ltd

Financing U.S. Graduate Medical Education: A Policy Position Paper of the Alliance for Academic Internal Medicine and the American College of Physicians

In this position paper, the Alliance for Academic Internal Medicine and the American College of Physicians examine the state of graduate medical education (GME) financing in the United States and recent proposals to reform GME funding. They make a series of recommendations to reform the current funding system to better align GME with the needs of the nation's health care workforce. These recommendations include using Medicare GME funds to meet policy goals and to ensure an adequate supply of physicians, a proper specialty mix, and appropriate training sites; spreading the costs of financing GME across the health care system; evaluating the true cost of training a resident and establishing a single per-resident amount; increasing transparency and innovation; and ensuring that primary care residents receive training in well-functioning ambulatory settings that are financially supported for their training roles

Genetic damage and cell cycle perturbations: biomarkers of effect in natural populations

Due to the character of the original source materials and the nature of batch digitization, quality control issues may be present in this document. Please report any quality issues you encounter to [email protected], referencing the URI of the item.Includes bibliographical references.Issued also on microfiche from Lange Micrographics.Spleen tissue from prairie voles (Microtus ochrogaster) and white-footed mice (Peromyscus leucopus) was analyzed using flow cytometry to assess possible genetic damage and cell cycle disruptions following exposure to radionuclides and nitroaromatic contamination at Weldon Spring Training Area in eastern Missouri. Rodents were trapped within areas contaminated with radionuclides (RAD) and nitroaromatics (TNT), as well as within nearby uncontaminated areas (Control). Male prairie voles from both RAD and TNT groups had a significantly lower proportion of cells in the G2+Metaphase portion of the cell cycle than males from the Control group and females from Control, RAD, and TNT groups. White-footed mice, both males and females, from the TNT group had a significantly higher proportion of cells in the G2+Metaphase portion of the cell cycle than mice from the Control group. In addition, male white-footed mice from the Control group had a significantly higher proportion of cells in the S-phase of the cell cycle than males from the TNT group and females from both Control and TNT groups. These results indicate cell cycle disruptions are caused by exposure to nitroaromatics and radionuclides, and physiological and ecological differences probably account for the male-specific responses observed in both species of rodent. These differences may reflect a gender bias in the ability to tolerate contaminants

Intron 7 (FGB-I7) of the fibrinogen, B beta polypeptide (FGB) : a nuclear DNA phylogenetic marker for mammals /

no.219 (2003

Correlations of Biomarkers and Self-Reported Seafood Consumption among Pregnant and Non-Pregnant Women in Southeastern Louisiana after the Gulf Oil Spill: The GROWH Study

Seafood contains health-promoting fatty acids, but is often contaminated with mercury (Hg), complicating recommendations and choices around fish consumption during pregnancy. Self-reported diet may be subject to inaccuracy and this inaccuracy could differ according to pregnancy status. We investigated correlations between self-reported seafood consumption and blood levels of Hg and n-3 polyunsaturated fatty acids (PUFAs) in women affected by the Deepwater Horizon oil spill. Spearman correlation coefficients were calculated comparing log blood Hg and n-3 PUFAs to seafood consumption, then stratified by pregnancy status. Crude and adjusted linear regression models were constructed using biomarkers of Hg and n-3 PUFA and seafood consumption, adjusting for age and pregnancy status. Weak but significant correlations were found between log Hg levels and intake of Hg-containing seafood ( r = 0.15) and were slightly stronger among pregnant women ( r = 0.22, vs. r = 0.10). Biomarkers for n-3 PUFAs were significantly correlated with seafood consumption ( r = 0.12). Hg-containing seafood consumption was associated with increased blood level Hg in the highest quartile in both unadjusted (β = 0.34, 95% CI: 0.15–0.53) and adjusted models (β = 0.28, 95% CI: 0.08–0.48). Self-reported seafood consumption was correlated with biomarkers of both n-3 PUFA and Hg, but this association was different when stratified by pregnancy status. Pregnant women may have better recall of Hg-containing seafood compared to nonpregnant women