Papers of the Month
By Sara Mishamandani Amolegbe
The BPA substitute BPS may harm egg cells
In an NIEHS-funded study, researchers demonstrated that bisphenol S (BPS), a replacement for bisphenol A (BPA), disrupts fertility and damages egg cells in animal models. When they compared BPA and BPS, the researchers found that the negative effects of BPS on reproductive function were seen at lower doses than BPA and involved different genetic mechanisms.
Concerns about the safety of BPA, a chemical in plastics and other products, has led to BPA-free goods, but also to use of similar alternatives such as BPS. To compare the effects of both chemicals on the reproductive system, researchers used Caenorhabditis elegans (C. elegans), or roundworms, a common laboratory model organism. They found that exposure to either chemical, or both chemicals, led to decreased fertility and damaged egg cells. BPS exposure also led to a stronger reproductive and DNA damage repair gene response than did BPA. These results suggest that BPS may damage the reproductive system more.
The researchers also found genetic differences in how both chemicals change reproductive functions in C. elegans. To confirm that changes were not unique to the model organism, they conducted an analysis of data from Toxcast, a mammalian toxicity database. This analysis also indicated that BPA and BPS affected some biological pathways differently.
The researchers suggested that BPS might not be a safe alternative to BPA. They emphasized the need for safety assessments of alternatives before they are used as replacements.
Chen Y, Shu L, Qiu Z, Lee DY, Settle SJ, Que Hee S, Telesca D, Yang X, Allard P. 2016. Exposure to the BPA-substitute bisphenol S causes unique alterations of germline function. PLoS Genet 12(7):e1006223.
Air pollution tied to shorter lung cancer survival time
Exposure to air pollution is associated with a shorter lifespan in patients after a lung cancer diagnosis, according to an NIEHS-funded study. Researchers observed that the median survival for people diagnosed with early stage lung cancers was approximately three years shorter for those who lived in areas with high regional pollution compared with those who lived in areas of lower regional pollution.
The scientists looked at the lung cancer data of more than 350,000 patients in the California Cancer Registry who were diagnosed with lung cancer between 1988 and 2009. The team estimated air pollutant levels for each patient based on their residence and cancer follow-up period. Estimates were based on California air pollutant data, which included levels of nitrogen dioxide, ozone, and particulate matter.
Air pollution had the greatest effect on survival in people diagnosed with early stage adenocarcinoma, the most common type of lung cancer. Patients diagnosed with early stage lung cancer had an average survival time of about 2.4 years in high pollution areas compared with 5.7 years in patients in low exposure areas. For these early stage patients, the researchers observed a higher risk of death with higher average nitrogen dioxide and particulate matter over the follow-up period after diagnosis.
The authors stated future studies should evaluate the effects of air pollution exposure reduction for lung cancer patients to improve outcomes, especially among patients who are diagnosed early.
Eckel SP, Cockburn M, Shu YH, Deng H, Lurmann FW, Liu L, Gilliland FD. 2016. Air pollution affects lung cancer survival. Thorax 71(10):891−898.
Mapping UV-induced DNA damage and repair
Researchers supported in part by NIEHS mapped the damage of ultraviolet (UV) radiation on DNA, providing an in-depth view of UV damage and repair on single units of DNA. Understanding the effects on DNA at such a high resolution could reveal how UV exposure leads to skin cancer and what could be done to prevent it.
Using a high-throughput sequencing method to map the yeast genome in greater detail than previous studies, researchers mapped cyclobutane pyrimidine dimers (CPDs), a common UV-induced form of DNA damage. With information at the single nucleotide, or DNA unit, level, the researchers looked for patterns of damage.
They found that DNA was more damaged when it faced away from histones, the structures that DNA wraps around inside the nucleus of a cell, protecting DNA facing inward. They also saw less damage around transcription factors, proteins that bind to specific stretches of DNA and regulate what genes are expressed in a cell. The researchers reported that repair of CPDs was much less efficient near positions in the DNA that are more important to expressing genes.
The findings provide new information about the roles of individual DNA units and transcription factors in response to UV damage and repair, providing insight into how UV radiation induces mutations that could lead to cancer.
Mao P, Smerdon MJ, Roberts SA, Wyrick JJ. 2016. Chromosomal landscape of UV damage formation and repair at single-nucleotide resolution. Proc Natl Acad Sci U S A 113(32):9057−9062.
New method for gene-environment interaction studies
NIEHS-funded researchers and colleagues developed a new approach to integrate multiple environmental exposures, analyzing the interactions between genes and the environment. Their new method creates an overall profile of exposures that can be compared to genetic differences and provides insight into the relationship among genes, environmental exposures, and complex diseases.
Most gene-environment interaction studies analyze the interactions involving one exposure at a time, which does not take into account the overall effects from multiple real-world exposures. Using the data from the Multi-Ethnic Study of Atherosclerosis, researchers demonstrated a two-step approach for modeling gene-environment interactions with multiple environmental factors. They used four common clustering and classification statistical strategies to combine information from multiple environmental factors, which allowed the team to create an overall exposure profile for each study participant. The researchers used this environmental exposure profile as a single variable to investigate how it interacts with different genes in an individual to influence health outcomes.
By combining information for multiple environmental exposures into one variable, researchers can discover how genes may modify the effect of a variety of different exposures examined together. The method can also guide development of questions and future studies by pointing out genetic differences and varied health outcomes based on certain combinations of exposures.
Ko YA, Mukherjee B, Smith JA, Kardia SL, Allison M, Diez Roux AV. 2016. Classification and clustering methods for multiple environmental factors in gene-environment interaction — application to the Multi-Ethnic Study of Atherosclerosis. Epidemiology; doi:10.1097/EDE.0000000000000548 [Online 29 July 2016].