Papers of the Month
By Sara Amolegbe
Greener neighborhoods linked to better heart health
Living in green neighborhoods may reduce the risk of cardiovascular disease by decreasing the body’s stress and boosting its ability to repair blood vessels, according to a new study by NIEHS grantees. Previous studies linking lower risk of cardiovascular disease with green spaces mainly relied on subjective questionnaires. This study is the first to provide direct evidence of physiological changes in people associated with living in green spaces.
The researchers measured biomarkers of cardiovascular disease in individuals who lived in neighborhoods with varying levels of greenness. The study participants included 408 outpatients from a preventive cardiology clinic. The greenness of their neighborhoods was estimated based on satellite data related to the coverage and density of vegetation.
Higher vegetation density within a 250-meter and 1-kilometer radius around participants’ residences were associated with lower urinary levels of a stress-related hormone called epinephrine. This effect was stronger in women, participants who were not taking blood pressure medications called beta-blockers, and individuals who had not previously experienced a heart attack.
Greenness was also linked to lower urinary levels of a molecule called F2‐isoprostane, a marker of oxidative stress, which suggested a link between green spaces and a decrease in oxidative stress. Blood cell measurements also revealed that living in green neighborhoods was associated with a better capacity for wound healing and repairing blood vessels.
Citation: Yeager R, Riggs DW, DeJarnett N, Tollerud DJ, Wilson J, Conklin DJ, O'Toole TE, McCracken J, Lorkiewicz P, Xie Z, Zafar N, Krishnasamy SS, Srivastava S, Finch J, Keith RJ, DeFilippis A, Rai SN, Liu G, Bhatnagar A. 2018. Association between residential greenness and cardiovascular disease risk. J Am Heart Assoc 7(24):e009117. (Story)
New houseplant enhances cleanup of air in homes
Scientists previously funded by NIEHS developed a houseplant that can remove chloroform and benzene from the air around it. Benzene in the home can originate from outside air, fuel storage in attached garages, and tobacco smoke. Chloroform can be released into the air in small amounts from water during showering.
The researchers genetically modified a common houseplant, pothos ivy, to express a protein called 2E1 that transforms these compounds into molecules the plants can use to support their own growth. The researchers made a synthetic version of the gene that expressed the rabbit form of 2E1 and introduced it into pothos ivy so that each cell in the plant expressed the protein.
The researchers tested how well their modified plants could remove the pollutants from air by putting the plants in glass tubes and adding either benzene or chloroform gas. The compared results for the modified plants with those from normal pothos ivy. For the unmodified plants, concentrations did not change over time for either gas. For the modified plants, the concentration of chloroform dropped by 82 percent after three days, and it was almost undetectable by day six. The benzene concentration dropped by about 75 percent by day eight.
According to the authors, they expect levels in homes to drop similarly if plants are inside an enclosure with something to move air past their leaves, like a fan. However, more work is needed to establish the practical usefulness of these plants in removing chloroform and benzene in the home.
Citation: Zhang L, Routsong R, Strand SE. 2018. Greatly enhanced removal of volatile organic carcinogens by a genetically modified houseplant, pothos ivy (Epipremnum aureum) expressing the mammalian cytochrome P450 2e1 gene. Environ Sci Technol 53(1):325–331.
Alkylating agents lead to unexpected DNA damage
NIEHS grantees discovered that monofunctional alkylating agents can form cross-links between DNA and histone proteins, a toxic form of DNA damage. Monofunctional alkylating agents are found in certain environmental pollutants as well as anticancer drugs, such as temozolomide.
The researchers studied the effect of monofunctional alkylating agents in free DNA and in nucleosome core particles, which serve as the protein-containing packaging material for DNA. They found that these chemicals can methylate DNA, forming N7-methyl-2′-deoxyguanosine (MdG). MdG has long been considered a benign lesion because of its minimal effects on DNA structure. However, this study showed that MdG is much more reactive in nucleosome core particles and forms unexpected cross-links with lysine residues in histone proteins. These cross-links are extremely toxic because they can block essential DNA functions such as replication and transcription.
The researchers observed these cross-links in engineered nucleosome core particles containing MdG at specific sites. They also observed the change in nucleosome core particles treated with the alkylating agent methyl methanesulfonate. According to the authors, most studies on MdG have been carried out in free DNA, so the discovery that MdG reactivity differs significantly in nucleosome core particles could have significant implications in how DNA alkylating agents play a role in cell toxicity.
Citation: Yang K, Park D, Tretyakova NY, Greenberg MM. Histone tails decrease N7-methyl-2'-deoxyguanosine depurination and yield DNA-protein cross-links in nucleosome core particles and cells. Proc Natl Acad Sci U S A 115(48):E11212–E11220.
Gut microbiome protects against arsenic toxicity
Microbes in the gut play an important role in protecting against arsenic toxicity in mice, according to a new NIEHS study. Researchers found that antibiotics disrupted the gut microbiome, allowing more arsenic to accumulate in organs, rather than being excreted. They also found that germ-free mice, which are mice raised without any microorganisms, excreted less and accumulated more arsenic compared to mice with conventional microbiomes.
The researchers also examined mice lacking the enzyme primarily responsible for arsenic detoxification in humans and other animals, known as As3mt. They found that these mice were even more sensitive to arsenic after antibiotic treatment or when raised without microorganisms, compared to mice with unaltered microbiomes. When they introduced organisms from the human microbiome to germ-free mice lacking As3mt, they found that certain transplanted microorganisms had a protective effect, depending on microbiome stability and the presence of specific bacteria, including Faecalibacterium.
The results demonstrated that functional As3mt and specific microbiome members are needed for protection against acute arsenic toxicity in mice. According to the authors, the results show that the gut microbiome may become an important explanatory factor of arsenic-induced diseases in humans and a novel target for prevention and treatment strategies.
Citation: Coryell M, McAlpine M, Pinkham NV, McDermott TR, Walk ST. 2018. The gut microbiome is required for full protection against acute arsenic toxicity in mouse models. Nat Commun 9(1):5424.
(Sara Amolegbe is a research and communication specialist for MDB Inc., a contractor for the NIEHS Division of Extramural Research and Training.)