Papers of the Month
Extramural
By Adeline Lopez
Correctional facilities' drinking water may put inmate health at risk
Arsenic concentrations in drinking water in Southwestern U.S. correctional facilities may be twice as high as those in nearby communities, according to a recent NIEHS-funded study. Although arsenic levels in drinking water are generally higher in the Southwest than the rest of the U.S., this is the first study to document disproportionate exposure to the substance from drinking water among inmates compared to non-incarcerated populations.
The research team analyzed more than 200,000 U.S. Environmental Protection Agency (EPA) arsenic monitoring records from nearly 40,000 community water systems from 2006 to 2011. They compared average arsenic concentrations in systems exclusively serving correctional facilities to all other water systems in the Southwest and the U.S. as a whole. They also determined the odds of exceeding the EPA's 10 micrograms per liter maximum contaminant level (MCL).
Average arsenic concentrations in correctional facility water systems were twice as high as other systems in the region and four times higher than water systems across the U.S. More than a quarter of correctional facility water systems exceeded the MCL, compared to just under 6% of other systems.
According to the authors, incarcerated people in the Southwestern U.S. are more likely to have higher levels of arsenic in their water, and may also lack access to alternative drinking sources, such as bottled water. Increased exposure to contaminants may also contribute to observed health disparities within this vulnerable population.
Citation: Nigra AE, Navas-Acien A. 2020. Arsenic in U.S. correctional facility drinking water, 2006–2011. Environ Res 188:109768.
Diesel exhaust linked to risk of Parkinson's disease
A new NIEHS-funded study uncovered the molecular mechanism by which exposure to diesel exhaust can damage brain cells and lead to behavioral deficits common in neurodegenerative conditions such as Parkinson’s disease.
Using zebrafish, the researchers studied how chemicals in diesel exhaust can alter neurons and influence behavior. They also looked at molecular activity in several pathways in the brain related to Parkinson's disease to understand how the chemicals affected the brain.
Zebrafish treated with diesel exhaust extract showed significantly less movement during light cycles and progressive loss of neurons compared to unexposed fish. In treated fish, the researchers reported fewer autophagosomes, which are molecular pouches that dispose of broken-down proteins in healthy neurons. This led to a toxic buildup of a protein called alpha-synuclein in the brain. Accumulation of alpha-synuclein is commonly seen in Parkinson’s patients. The team saw similar results when they looked at cultured human brain cells exposed to diesel exhaust.
Interestingly, when fish were also treated with nilotinib, a drug that helps cells break down and remove old proteins, diesel exhaust exposure no longer killed neurons. According to the authors, these results explain why long-term exposure to traffic-related air pollution increases neurodegenerative disease risk, and point to opportunities to identify therapies that protect the brain.
Citation: Barnhill LM, Khuansuwan S, Juarez D, Murata H, Araujo JA, Bronstein JM. 2020. Diesel exhaust extract exposure induces neuronal toxicity by disrupting autophagy. Toxicol Sci 176(1):193-202.
HLTF plays key role in DNA replication and genomic stability
A new NIEHS-funded study sheds light on how cells resolve DNA damage and maintain genomic stability during replication. Researchers identified the protein helicase-like transcription factor (HLTF) as a key regulator of the cellular replication stress response. The protein prevents genomic instability known to contribute to many diseases, such as cancer.
Using cells with and without HLTF, the researchers studied mechanisms and pathways by which cells overcome DNA replication stress, which can stall replication and cause genome instability. They used genetic and imaging approaches to identify which DNA damage tolerance pathways help replication progression.
The team found that in cells without HLTF, DNA replication did not slow down at the site of replication under stress. Instead, with increased resistance to replication stress, DNA replication continued unrestrained through other mechanisms. In this context, unrestrained replication can lead to a reduction in certain forms of DNA damage, possibly at the expense of reducing other such damage.
According to the authors, HLTF is important in regulating replication and preventing alternative mechanisms that can lead to potentially mutagenic forms of DNA replication related to tumor formation. Their findings also illustrate the adaptability of replication in responding to chemotherapy or other threats to genome integrity.
Citation: Bai G, Kermi C, Stoy H, Schiltz CJ, Bacal J, Zaino AM, Hadden MK, Eichman BT, Lopes M, Cimprich KA. 2020. HLTF promotes fork reversal, limiting replication stress resistance and preventing multiple mechanisms of unrestrained DNA synthesis. Mol Cell 78(6):1237-1251.
High PFAS levels tied to earlier menopause
High levels of per- and polyfluoroalkyl substances (PFAS) in the body may accelerate menopause in women, according to a new NIEHS-funded study. PFAS are synthetic chemicals found in many consumer products. The substances persist in the environment and have been linked with a variety of health problems.
The researchers analyzed serum levels of PFAS in a national sample of 1,200 U.S. women aged 45-56 years between 1999 and 2017. They evaluated the relationship between age of menopause and concentrations of seven individual PFAS and PFAS mixtures in serum.
For individual PFAS, all but one showed a significant relationship between increasing serum levels and earlier age of menopause. The median age of menopause was approximately one year earlier for women in the higher exposure groups compared to the lower exposure groups. The combined effect of PFAS was more pronounced, with women in the highest exposure group reaching menopause a full two years earlier than women in the lowest exposure group.
These results suggest that PFAS may play an important role in ovarian aging, perhaps through disrupting the endocrine system. According to the authors, menopause occurring even a few years earlier than normal can have significant effects on cardiovascular and bone health, quality of life, and overall health among women.
Citation: Ding N, Harlow SD, Randolph JF, Calafat AM, Mukherjee B, Batterman S, Gold EB, Park SK. 2020. Associations of perfluoroalkyl substances with incident natural menopause: the study of women's health across the nation. J Clin Endocrinol Metab; doi: 10.1210/clinem/dgaa303 [Online 3 June 2020].
(Adeline Lopez is a science writer for MDB Inc., a contractor for the NIEHS Division of Extramural Research and Training.)
