High throughput microscopy and image analysis technologies identify potentially safer substitutes for BPA

July 14, 2017
3D chemical structure of bisphenol A. Credit: Edgar181 via Wikimedia Commons

Researchers at Baylor College of Medicine have identified a group of potential substitutes for bisphenol A (BPA) that lack the adverse effects typically associated with BPA. The researchers used automated microscopy- and image analysis-based technologies that allowed them to analyze multiple effects of the compounds in hours, instead of days or weeks, that are usually required for standard toxicology analyses. The results are published in PLOS ONE.

"BPA, a poster child for , is a synthetic compound present in a wide range of products including polycarbonate plastics used in the manufacture of water and infant bottles, on resins coating metal food cans and in many other applications," said corresponding author Dr. Michael Mancini, professor of molecular and cellular biology, director of the Integrated Microscopy Core at Baylor and co-director of the John S. Dunn Gulf Coast Consortium for Chemical Genomics.

Health concerns about BPA and BPA substitutes have emerged because, according to a National Health and Nutrition Examination Survey, BPA is widespread in human populations. BPA can leach into canned foods or bottled water, and people are exposed when consuming those foods. Further concern comes from animal studies showing that even low-dose exposure to BPA during development can result in cancer and negative effects on fetuses and newborns.

BPA, like other endocrine disrupting chemicals, or EDCs, affects the body by interacting with the hormonal or endocrine system; in particular, researchers have studied the effects of BPA binding to estrogen receptors. With BPA and other EDCs in the environment, rapid and sensitive testing of compounds using new technology platforms is now available to identify compounds with potentially similar effects in living organisms.

"People are exposed to the various plastics that contain BPA or BPA substitutes on a daily basis, so finding compounds that would allow us to make these plastics safer is an important contribution," said first author Dr. Adam Szafran, an Instructor in the Mancini lab and chief architect of the custom imaging and image analysis platforms.

A powerful, fast experimental approach to screen potential BPA substitutes

Earlier, Mancini and his colleagues developed a new, powerful experimental approach that combined high throughput microscopy techniques with specifically engineered cell lines and roboticized screening resources to individually test the effect of numerous compounds on biological functions; these experiments are highly efficient, generating a large number mechanistic and phenotypic measurements simultaneously, even with only very brief exposure of compounds to cells.

"We previously established highly multiplexed, single cell-oriented model systems to identify mechanisms involved in complex hormonal biology," Mancini said. "Unlike standard biochemical or toxicological assays, our approach quantifies levels of estrogen receptors, nuclear localization, DNA binding, large-scale chromatin modeling, protein interactions and transcription, and also include data on toxicity, cell proliferation and many other characteristics; all at the level of individual cells and in one assay that only takes a few hours."

A robotic system processes the samples and takes tens of thousands of images of the cells through an automated microscope. Later, in-house developed software analyzed and reported on more than 10 billion data points to create a comprehensive picture of what is going on inside and on the surface of the cells.

"When the paper describing our novel approach was published, Valspar Corp., an industrial coatings company, approached our lab," Mancini said. "They were interested in finding a compound that does not have activity on estrogen receptors, but still provides a means to extend the shelf life of canned foods. Traditional toxicology studies conducted in animals are time consuming, expensive and provide limited data regarding the mechanism involved. Our approach is much faster, sensitive and accurate as standard biochemical assays and allows for testing for numerous compounds at once."

The researchers used their automated approach to screen a number of BPA substitute candidates for their ability to bind to estrogen receptors and trigger their activity.

"Using our high-throughput assay, we identified two compounds that are relatively inactive when compared to the negative effects attributed to BPA or the BPA-substitutes in use today," Szafran said.

"The we found passed our testing, but it doesn't mean that they are completely free of effects," Mancini said. "This would need further testing in animal studies."

Explore further: House dust spurs growth of fat cells in lab tests

More information: Adam T. Szafran et al. Characterizing properties of non-estrogenic substituted bisphenol analogs using high throughput microscopy and image analysis, PLOS ONE (2017). DOI: 10.1371/journal.pone.0180141

Related Stories

House dust spurs growth of fat cells in lab tests

July 12, 2017
Poor diet and a lack of physical activity are major contributors to the world's obesity epidemic, but researchers have also identified common environmental pollutants that could play a role. Now one team reports in ACS' journal ...

Endocrine disrupters: potentially harmful chemicals for human hormones

July 5, 2017
Potentially harmful chemicals which can interfere with the normal functioning of human hormones are known as endocrine disruptors (EDs).

Exposure to BPA substitute, BPS, multiplies breast cancer cells

April 2, 2017
Bisphenol S (BPS), a substitute for the chemical bisphenol A (BPA) in the plastic industry, shows the potential for increasing the aggressiveness of breast cancer through its behavior as an endocrine-disrupting chemical, ...

Recommended for you

Across Asia, liver cancer is linked to herbal remedies: study

October 18, 2017
Researchers have uncovered widespread evidence of a link between traditional Chinese herbal remedies and liver cancer across Asia, a study said Wednesday.

Eating better throughout adult years improves physical fitness in old age, suggests study

October 18, 2017
People who have a healthier diet throughout their adult lives are more likely to be stronger and fitter in older age than those who don't, according to a new study led by the University of Southampton.

Global calcium consumption appears low, especially in Asia

October 18, 2017
Daily calcium intake among adults appears to vary quite widely around the world in distinct regional patterns, according to a new systematic review of research data ahead of World Osteoporosis Day on Friday, Oct. 20.

New study: Nearly half of US medical care comes from emergency rooms

October 17, 2017
Nearly half of all US medical care is delivered by emergency departments, according to a new study by researchers at the University of Maryland School of Medicine (UMSOM). And in recent years, the percentage of care delivered ...

Experts devise plan to slash unnecessary medical testing

October 17, 2017
Researchers at top hospitals in the U.S. and Canada have developed an ambitious plan to eliminate unnecessary medical testing, with the goal of reducing medical bills while improving patient outcomes, safety and satisfaction.

No evidence that widely marketed technique to treat leaky bladder/prolapse works

October 16, 2017
There is no scientific evidence that a workout widely marketed to manage the symptoms of a leaky bladder and/or womb prolapse actually works, conclude experts in an editorial published online in the British Journal of Sports ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.