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Environmental Factor

Environmental Factor

Your Online Source for NIEHS News

June 2021

Papers of the month

New approach sheds light on PFAS in coastal watersheds

NIEHS-funded researchers developed a new tool to identify and characterize previously undetected per- and polyfluoroalkyl substances (PFAS) in watersheds on Cape Cod, Massachusetts. The team identified a distinct signature for PFAS from aqueous film forming foam (AFFF), which is used in firefighting and can contaminate drinking water. However, a large fraction of fluorine could not be explained by AFFF.

PFAS are a large group of compounds that have a carbon-fluorine backbone but vary in other chemical characteristics, such as carbon chain length. In the environment, some PFAS change and transform, making it difficult to identify the parent compound and its source.

The team collected water samples from six coastal watersheds, three of which had known sources of AFFF contamination, and designed an approach to distinguish signatures of PFAS from different sources. First, they analyzed samples for 27 common PFAS compounds using mass spectrometry. Using a method called the total oxidizable precursor (TOP) assay, they developed a new statistical approach to reconstruct the chain length, and therefore source, of the parent compound.

They detected 13 of the 27 common PFAS in more than 70% of the samples. Concentrations of these PFAS were 17 times higher in watersheds with a known AFFF source compared to those without one. The researchers saw distinct clustering in PFAS signatures based on the presence or absence of known AFFF sources. To identify PFAS not captured by TOP analysis, they measured organofluorines, or compounds that contain the carbon-fluorine bond, revealing high concentrations of unexplained organofluorine that did not originate from AFFF.

According to the authors, traditional approaches fail to explain substantial fractions of organofluorine in watersheds, representing a gap in our understanding of PFAS sources that could affect aquatic life and seafood consumers.

CitationRuyle BJ, Pickard HM, LeBlanc DR, Tokranov AK, Thackray CP, Hu XC, Vecitis CD, Sunderland EM. 2021. Isolating the AFFF signature in coastal watersheds using oxidizable PFAS precursors and unexplained organofluorine. Environ Sci Technol 55(6):3686-3695.

New marker of COVID-19 severity points to potential therapies

Certain fatty acids in the blood of COVID-19 patients may predict the severity of adult respiratory distress syndrome (ARDS) and offer a target for treatment, according to a new NIEHS-funded study. ARDS involves a buildup of fluid in the lungs and is a leading cause of death in COVID-19 patients.

In a pilot study, researchers examined six COVID-19 patients and found higher blood levels of certain fatty acids compared to healthy individuals. These fatty acids, called leukotoxins and leukotoxin diols, play a role in inflammatory disease and ARDS but have never been studied for their role in respiratory complications related to COVID-19 until now.

The scientists found that changes in leukotoxin diol concentrations and the ratio between leukotoxins and leukotoxin diols could be used to identify which samples came from COVID-19 patients. Leukotoxins come from linoleic acid, an abundant fat in the body, and are converted to leukotoxin diols by an enzyme called soluble epoxide hydrolase.

According to the researchers, conversion of fatty acids to the toxic leukotoxin diols may contribute to respiratory complications in COVID-19 patients and serve as a biomarker for ARDS severity among such patients. On the other hand, soluble epoxide hydrolase may represent a therapeutic target to reduce creation of leukotoxin diols and respiratory complications.

CitationMcReynolds CB, Cortes-Puch I, Ravindran R, Khan IH, Hammock BG, Shih PB, Hammock BD, Yang J. 2021. Plasma linoleate diols are potential biomarkers for severe COVID-19 infections. Front Physiol 12:663869.

Researchers pinpoint molecular trigger for lung fibrosis

A new NIEHS-funded study revealed a series of molecular steps that lead to severe scarring in the lungs, called idiopathic pulmonary fibrosis (IPF), in response to environmental exposures. The key step involves a modified version of vimentin, a structural protein that usually maintains cellular integrity.

The researchers combined studies in mice and humans with lung fibrosis to uncover the mechanism by which exposure to cadmium and carbon black in particulates damages the lungs. They also leveraged a three-dimensional model, called a pulmosphere, which uses lung tissue from humans to create a realistic representation of the cell types and relationships present in the human lung.

Lung tissue of IPF patients had higher levels of carbon black and cadmium compared to healthy controls. Cadmium concentrations were directly proportional with levels of the modified version of vimentin, called citrullinated vimentin (Cit-Vim). Exposure to cadmium and carbon black stimulated production of Cit-Vim in lung macrophages from IPF patients and in mice.

In pulmospheres, Cit-Vim activated invasive connective tissue cells called fibroblasts and increased the expression of collagen, both key components of lung scarring in fibrosis. Mice treated with Cit-Vim developed a similar pattern of fibrosis, but those lacking a key enzyme called PAD2 had lower amounts of Cit-Vim and lower incidence of lung fibrosis compared to mice with the enzyme.

According to the authors, lung macrophages generate Cit-Vim in response to environmental exposure, which in turn triggers cellular events leading to fibrosis. However, PAD2 may offer a promising target for treatment.

CitationLi FJ, Surolia R, Li H, Wang Z, Liu G, Kulkarni T, Massicano AVF, Mobley JA, Mondal S, de Andrade JA, Coonrod SA, Thompson PR, Wille K, Lapi SE, Athar M, Thannickal VJ, Carter AB, Antony VB. 2021. Citrullinated vimentin mediates development and progression of lung fibrosis. Sci Transl Med 13(585):eaba2927.

DNA repair enzyme controls switch from cancer to tissue damage

NIEHS-funded researchers discovered a DNA-repair molecule that affects susceptibility to disease in mice exposed to N-nitrosodimethylamine (NDMA). Alkyladenine DNA glycosylase (AAG) is known to be an important player in DNA repair, but this study revealed for the first time that too much or too little can control the switch between cancer and lethality.

NDMA is a DNA-damaging agent found in chemical waste and produced as a byproduct of certain wastewater treatment processes. The team previously developed a specialized mouse model to compare mice with deficient or overexpressed AAG for DNA and tissue damage, mutations, and cancer resulting from NDMA exposure. They also integrated a suite of molecular, cellular, and physiological analyses to explore the underlying mechanisms involved.

Mice deficient in AAG had more DNA mutations and cancer when exposed to NDMA than normal mice. Mice with high levels of AAG were protected from mutations and cancer following NDMA exposure but had more tissue damage and lower survival rates than normal mice. NDMA exposure also damaged DNA in normal mice, but they seemed to be somewhat protected from the extremes associated with too much or too little AAG.

According to the authors, AAG controls whether cells survive DNA damage and whether they will eventually develop mutations and cancer. They explained that these findings may help identify low- or high-risk populations since humans vary by as much as 20-fold in AAG activity levels, and may be useful to inform precision medicine to treat cancer.

CitationKay JE, Corrigan JJ, Armijo AL, Nazari IS, Kohale IN, Torous DK, Avlasevich SL, Croy RG, Wadduwage DN, Carrasco SE, Dertinger SD, White FM, Essigmann JM, Samson LD, Engelward BP. 2021. Excision of mutagenic replication-blocking lesions suppresses cancer but promotes cytotoxicity and lethality in nitrosamine-exposed mice. Cell Rep 34(11):108864.

(Adeline Lopez is a research and communication specialist for MDB Inc., a contractor for the NIEHS Division of Extramural Research and Training.)

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