By: Nour Hany
In our everyday life, we deal with a huge amount of chemicals, some of which are harmful, such as toxins and pollutants, while others are harmless, such as water or air. To understand how these toxic chemicals impact our health and wellbeing, researchers released “the Comparative Toxicogenomics Database” in an effort to understand this significant connection.
Back in the day, researchers used to conduct their studies with a low-throughput analysis, which means that they only focused on a single gene to understand the impact of chemical exposure on our health. However, in a recent study from a University of Massachusetts Amherst environmental health scientist, a new approach has been taken to tackle this issue from a completely different perspective.
The study was directed towards understanding the interaction of chemicals, pollutants, and pharmaceuticals; how they affect human health, and their role in gene expression. “When we identified all the sensitive genes, we were very much surprised that almost every well-known molecular pathway is sensitive to chemicals to a certain degree”. Said Alexander Suvorov, Study Lead Author, and Associate Professor, School of Public Health and Health Sciences, University of Massachusetts Amherst.
Suvorov and a team of five undergraduate and graduate students—Victoria Salemme, Joseph McGaunn, Menna Teffera, Anthony Poluyanoff, and Saira Amir—collected data concerning chemical-gene interactions, including human, rat, and mouse genes from the Comparative Toxicogenomics Database. The study was conducted using high-throughput gene expression analysis, in which they “created a database of 591,084 chemical-gene interactions reported in 2,169 studies”.
High-throughput analysis means that they looked at multiple genes instead of focusing on single gene studies as was done before. “In the recent past, everything that we knew about molecular mechanisms affected by chemicals was coming from low-throughput experiments,” Suvorov said.
Approach
The researchers involved in this study gathered interactions that analyzed 1,239 unique chemicals and encompassed 17,338 unique genes. They split their chemicals database into two parts: The first part was pharmaceutical chemicals, designed to look for and target known molecular cascades; the second part of the chemicals database included other chemicals, such as cosmetics, agricultural, pollutants, and industrial.
Results
The study included a comparison of the sensitivity of genes and molecular pathways to “non-biologically active” and “biologically active” chemicals, in a way to test if the researchers' identification of molecular mechanisms that are sensitive to chemical exposures may be muddled if they included chemicals that are “intentionally designed to target specific molecular pathways in mammalian cells”. After comparing “the number of chemical-gene interactions for every gene in the BA and NBA subsets of the database,” the result indicated that the values of the chemical-gene interaction were similar in both of these subsets.
The new findings of this study highlighted the pathways involving lipid metabolism, autoimmune disease, cancer, and aging, and how they are also highly sensitive to chemical exposures, which puts the possibility that chemical exposures might have a role in conditions, such as fatty liver disease, lupus, and rheumatoid arthritis, diabetes, and many others. It is worth mentioning that pathways responsible for stress and damage are also highly sensitive to chemical exposures. “This study represents a significant step forward in the use of genomic data for the improvement of public health policies and decisions,” Suvorov says, “and the public health field will benefit from a future focus of toxicological research on these identified sensitive mechanisms”.
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