Publicity to Man-Made Chemical substances Influences Genes Controlling Getting older, Immune System and Metabolism
By Alexander Suvorov, University of Massachusetts Amherst
Today people are exposed to thousands of man-made chemicals. However, the effects on people’s health are not fully understood.
In 2020, the number of chemicals registered reached 167 million. People are exposed to them every day through food, water, contaminated air, medicines, cosmetics, and other man-made substances. Less than 1% of these chemicals have been tested for toxicity, and those that have been tested show the ability to interfere with almost every biological process in our bodies. Can we infer from this how cumulative exposures affect our health?
I am an environmental toxicologist who studies the effects of man-made chemicals on our health. I decided to develop a computational approach to objectively compare the sensitivity of all genes to all chemicals and identify the most vulnerable biological processes.
For our study, my research colleagues and I used data from the Comparative Toxicogenomic Database. The Comparative Toxicogenomic Database gathers information from thousands of published studies on how chemicals alter the activity of genes. Genes are sections of DNA that code for proteins that fulfill a wide range of functions in cells, from the construction of tissues to the metabolism of nutrients. When chemicals affect genes, it leads to increased or decreased production of proteins.
Modern molecular biology methods can detect changes in the activity of all genes in the genome in response to a chemical insult. I developed an approach that superimposed lists of altered genes from different studies to calculate how often each gene was affected. The resulting numbers reflect the sensitivity of genes to chemicals in general.
Using 2,169 studies in mice, rats, humans, and their cells, my research group assessed the sensitivity of 17,338 genes to chemical exposure. These studies tested the effects of 1,239 different chemicals, ranging from prescription drugs to environmental pollutants.
The next step was to run tests to make sure this sample of over 1,000 chemicals was large enough to reliably represent all classes of man-made chemicals that humans are exposed to. To do this, we measured the sensitivity of genes for one half of this list and then for another to test whether even a smaller number of chemicals can reliably identify sensitive genes. The results were encouraging – the gene sensitivity values were nearly identical in both studies.
The cellular defense system reacts to chemicals
Our cells are not completely helpless when exposed to chemical abuse. In fact, they have strategies for dealing with the stress and damage caused by chemicals. Our data confirm that these protective measures act in response to exposure.
This line of defense includes enzymes that eliminate toxic chemicals, alleviate oxidative stress (the build-up of reactive radicals in cells), repair damaged DNA and proteins, and identify severely damaged cells to trigger their death and prevent them from becoming cancerous.
All molecular pathways are sensitive to chemicals
Overall, we’ve found that almost every known pathway can be affected by chemicals. This finding has significant implications for regulatory toxicology.
With the ever-increasing number of man-made chemicals, society needs to develop quick and inexpensive methods for toxicity testing.
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An important question that remains unanswered is which avenues should be covered by testing to ensure that regulators do not allow chemicals that damage or disrupt critical molecular circuitry. Our data suggests that we need to develop tests that cover every known molecular pathway without exception.
Our study outlines new priorities for toxicological research, including the role of chemical exposures on metabolic health, the immune system, development, and aging.
Alexander Suvorov, Assistant Professor, University of Massachusetts Amherst
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