Papers of the Month
By Sara Amolegbe
Early-life exposure to fracking chemicals may damage immune system
Prenatal exposure to chemicals used in unconventional oil and gas (UOG) extraction, also known as fracking, affected immune system development in mice, according to a new study by NIEHS grantees. The study provided the first evidence that early-life exposure to a mixture of 23 commonly used UOG chemicals may hinder the ability to ward off diseases later in life.
Researchers added the UOG mixture or a control substance without UOG chemicals to the drinking water of pregnant mice. Chemical doses were equivalent to exposure estimates from levels detected in groundwater in UOG production regions. After the pups were born, the team analyzed outcomes related to infections, allergies, and autoimmune diseases.
The researchers reported that developmental exposure led to several changes in the cells of the immune system and affected the composition and function of T cells, which are essential to clearing infections, including many caused by viruses. These effects on T cells were more severe in female offspring. Prenatal exposure to the UOG mixture also expedited and worsened autoimmune disease symptoms in female but not male offspring.
According to the authors, their results suggested that developmental exposure to UOG chemicals may lead to long-lasting changes in the mouse immune system, particularly in females, and more research is needed to examine the potential risk of immune dysfunction in people living near UOG operations.
Citation: Boule LA, Chapman TJ, Hillman SE, Kassotis CD, O’Dell C, Robert J, Georas SN, Nagel SC, Lawrence BP. 2018. Developmental exposure to a mixture of 23 chemicals associated with unconventional oil and gas operations alters the immune system of mice. Toxicol Sci; doi:10.1093/toxsci/kfy066 [Online 01 May 2018].
Kitchen cabinets emit potentially harmful PCBs
NIEHS grantees discovered that finished cabinetry is a predominant and previously unknown source of airborne polychlorinated biphenyls (PCBs) in residential homes.
As a group, PCBs are classified as human carcinogens, and their manufacture has been banned in the United States since 1979. However, they are still found in the environment because of widespread historical sources and inadvertent production as manufacturing byproducts. To determine levels of PCBs present in and around homes, researchers collected samples of airborne PCBs using passive air samplers for a 6-week interval inside and outside 16 homes in Iowa. From the air samples, they determined air concentrations of all 209 forms of PCBs.
They found that the PCB forms PCB 47, PCB 51, and PCB 68 accounted for up to 50 percent of measured indoor PCBs and at much higher levels than expected, with higher concentrations in recently-built houses.
After testing emissions from a variety of household items, including the stove, floor, and walls, they identified finished kitchen cabinetry as the major source of these three forms of PCBs. According to the study, the researchers suspected that the substances came from the decomposition of 2,4-dichlorobenzoyl peroxide, which is commonly found in modern cabinet sealants.
Citation: Herkert NJ, Jahnke JC, Hornbuckle KC. 2018. Emissions of tetrachlorobiphenyls (PCBs 47, 51, and 68) from polymer resin on kitchen cabinets as a non-aroclor source to residential air. Environ Sci Technol 52(9):5154–5160.
Assessing toxicity of metal oxide nanoparticles
By examining the toxicological profile of 29 metal oxide nanoparticles, NIEHS grantees demonstrated that certain types of nanoparticles are more toxic to liver cells, and that different nanoparticles may lead to changes in different types of cells. The study provided a reference grid for toxicity screening of metal oxide nanoparticles, which are among the most abundant engineered nanomaterials produced. They are used in personal care products, clothing, and other consumer goods.
Researchers studied the effects of an array of metal oxide nanoparticle exposures on liver cells, including Kupffer cells, which play a key role in clearing out bacteria and cell debris, and hepatocytes, which primarily perform metabolic and detoxification functions. They found that transition metal oxides and rare earth oxides, two types of redox-active and highly soluble metal oxides, were the most toxic to liver cells. Although exposure to transition metal oxides led to cell death in both cell types, exposure to rare earth oxides only led to cell death in Kupffer cells.
The findings compared the toxicological profiles of an extensive range of metal oxide nanoparticles in Kupffer cells and hepatocytes and demonstrated differences in cell viability and inflammatory responses. According to the authors, these mechanistic considerations could be used to evaluate the safety of metal oxides, including commercial products developed from these materials.
Citation: Mirshafiee V, Sun B, Chang CH, Liao YP, Jiang W, Jiang J, Liu X, Wang X, Xia T, Nel AE. 2018. Toxicological profiling of metal oxide nanoparticles in liver context reveals pyroptosis in Kupffer cells and macrophages versus apoptosis in hepatocytes. ACS Nano 12(4):3836–3852.
Role of PXR protein in early-life BPA exposure and atherosclerosis
NIEHS grantees provided mechanistic evidence linking maternal bisphenol A (BPA) exposure to an increased risk of atherosclerosis, which is the narrowing of arteries due to plaque buildup, in offspring. The findings in mice showed how BPA could activate the pregnane X receptor (PXR), a protein in humans that detects foreign substances in the body and regulates several genes involved in metabolizing them.
Previous studies have shown that PXR activation can accelerate atherosclerosis development in mice. Although BPA has been shown to activate PXR in human cells, it does not activate PXR in mice or rats. To investigate the effects of BPA on atherosclerosis in mice, the researchers developed an atherosclerosis-prone mouse model with human-like PXR. They compared the effects of BPA exposure in atherosclerosis-prone mice with and without the humanized PXR.
The researchers reported that exposure to BPA around birth increased atherosclerosis in atherosclerosis-prone adult male, but not female, PXR-humanized mice. In these mice, they also observed increased expression of the fatty acid transporter CD36, which is a direct PXR target gene that plays a role in atherosclerosis development.
According to the authors, the study is the first to report the effect of maternal BPA exposure on atherosclerosis development in male offspring. Because PXR can be activated by endocrine-disrupting chemicals other than BPA, the authors added that activation of human PXR should be considered when assessing the risk of endocrine-disrupting chemicals.
Citation: Sui Y, Park SH, Wang F, Zhou C. 2018. Perinatal bisphenol A exposure increases atherosclerosis in adult male PXR-humanized mice. Endocrinology 159(4):1595–1608.
(Sara Amolegbe is a research and communication specialist for MDB Inc., a contractor for the NIEHS Division of Extramural Research and Training.)