Papers of the Month
By Sara Amolegbe
Study of Medicare records links air pollution and mortality
An NIEHS-funded study of people who received Medicare showed that long-term exposure to ambient fine particulate matter (PM2.5) and ozone may increase the risk of premature death. Both are components of air pollution, and the risk occurred even at levels below the
National Ambient Air Quality Standards.
The researchers examined Medicare claim records for the entire Medicare population of 60 million Americans age 65 years and older. They also estimated air pollution levels for every square kilometer in the U.S. The exposure data was then overlaid with the Medicare health records data. The team used a well-validated exposure prediction model that allowed them to include study participants who lived in unmonitored and less-populated areas.
The researchers reported a linear connection between ozone concentration and mortality. Based on their estimates, lowering ozone by 1 part per billion nationwide could save about 1,900 lives each year. Lowering PM2.5 by 1 microgram per cubic meter nationwide could save about 12,000 lives per year.
The enormous sample size also allowed the researchers to estimate risk among racial minorities and disadvantaged subgroups. The researchers found that men, blacks, and low-income groups were at higher risk from PM2.5 exposure compared with the national average. Blacks had mortality risks three times higher than the national average. The team also observed differences in the health effects of PM2.5 exposure between people in urban and rural settings, which could be due to differences in the particulate composition.
Di Q, Wang Y, Zanobetti A, Wang Y, Koutrakis P, Choirat C, Dominici F, Schwartz JD. 2017. Air pollution and mortality in the Medicare population. N Engl J Med 376(26):2513–2522.
Ozone pollution linked to cardiovascular disease
A new study, funded in part by NIEHS, revealed a link between exposure to ozone and health changes that may lead to cardiovascular disease. Adverse cardiovascular effects were observed with ozone levels lower than those known to affect respiratory health and levels lower than current U.S. Environmental Protection Agency (EPA) air quality standards.
For 2 months, researchers studied 89 healthy adults who lived on a work campus in China. They measured indoor and outdoor ozone levels, along with other pollutants. At four intervals, the study team took participant blood and urine samples and used a breathing test to examine inflammation and oxidative stress, arterial stiffness, blood pressure, clotting factors, and lung function in participants.
At ozone concentrations lower than levels known to influence pulmonary function, researchers found an association between increased ozone levels and blood platelet activation, which is a risk factor for clotting, as well as increased blood pressure. Both blood platelet activation and blood pressure are associated with increased risk for many cardiovascular diseases.
The findings revealed possible mechanisms by which ozone might affect cardiovascular health. According to the authors, the standard for safe ozone exposure should consider its association with cardiovascular disease risk, which may occur at lower levels of ozone than respiratory effects.
Day DB, Xiang J, Mo J, Li F, Chung M, Gong J, Weschler CJ, Ohman-Strickland PA, Sundell J, Weng W, Zhang Y, Zhang JJ. 2017. Association of ozone exposure with cardiorespiratory pathophysiologic mechanisms in healthy adults. JAMA Intern Med; doi: 10.1001/jamainternmed.2017.2842 [Online 17 July 2017].
Potentially safer alternatives to BPA identified
NIEHS-funded researchers and colleagues have identified a group of potential substitutes for bisphenol A (BPA). These compounds demonstrate low potential for affecting estrogenic or androgenic endocrine activity, which means they are less likely to disrupt hormones produced by the body.
Previous studies indicated that BPA is an endocrine disrupting chemical, which has garnered attention because of the widespread use of BPA in consumer products. Health and environmental concerns about the safety of BPA have led to a search for materials without similar effects on endocrine activity.
The researchers screened BPA substitute candidates for their ability to bind to hormone receptors and trigger activity. They used a novel automated approach that included taking tens of thousands of images of cells exposed to the chemicals and analyzing more than 10 billion data points. With a comprehensive picture of what occurred inside and on the surface of the cells, the researchers were able to assess effects of the compounds in hours, instead of the days or weeks usually required for standard toxicology analyses.
In this study, bisguaiacol F, tetramethyl bisphenol F epoxy resin, and tetramethyl bisphenol F diglycidyl ether demonstrated low potential for affecting estrogenic or androgenic endocrine activity. Although further research is needed to assess other potential effects of these compounds, the authors suggest that they could be potentially viable alternatives to BPA.
Szafran AT, Stossi F, Mancini MG, Walker CL, Mancini MA. 2017. Characterizing properties of non-estrogenic substituted bisphenol analogs using high throughput microscopy and image analysis. PLoS One 2017 Jul 12(7):e0180141.
How epigenetic alterations contribute to inflammation-driven cancer
NIEHS grantees and colleagues reported a mechanism by which epigenetics, which refers to changes in the way genetic information and proteins are expressed without directly changing the sequence of DNA, may be involved in inflammation-induced tumor development. The team found that epigenetic alterations initiated by inflammation and proteins that correct mismatched base pairs after DNA replication may prevent the expression of tumor suppressor genes.
In mice, the researchers observed that the loss of a specific mismatch repair protein, MutS homolog 2, put an end to the epigenetic alterations observed in inflammation-induced tumors. In addition, they found that tumors induced by inflammation had higher methylation at DNA regions associated with tumor suppressor genes compared with tumors not induced by inflammation.
The team reported that genes with increased DNA methylation exhibited reduced expression at time points that coincided with peak levels of DNA damage associated with inflammation. DNA regions with increased methylation were consistent between inflammation-induced tumors from different mice, suggesting a similarity in the genes whose expression is regulated by DNA methylation.
Approximately 25 percent of all cancers are associated with chronic inflammation. According to the authors, understanding these mechanisms may help the scientific community therapeutically target inflammation-induced epigenetic changes and potentially reduce cancer risk in people with chronic inflammatory diseases.
Maiuri AR, Peng M, Sriramkumar S, Kamplain CM, DeStefano Shields CE, Sears CL, O'Hagan HM. 2017. Mismatch repair proteins initiate epigenetic alterations during inflammation-driven tumorigenesis. Cancer Res 77(13):3467–3478.
(Sara Amolegbe is a research and communication specialist for MDB Inc., a contractor for the NIEHS Division of Extramural Research and Training.)