Exposure to Man-Made Chemicals Influences Genes Controlling Aging, Immune System and Metabolism

By Alexander Suvorov, University of Massachusetts Amherst

Today humans are exposed to thousands of man-made chemicals. Yet the effects on people’s health are still not fully understood.

In 2020 the number of registered chemicals reached 167 million. Every day people are exposed to them through food, water, contaminated air, drugs, cosmetics and other man-made substances. Less than 1% of these chemicals were tested for toxicity, and those that were tested demonstrate ability to disrupt almost every biological process in our body. Can we infer how cumulative exposures shape our health?

I am an environmental toxicologist studying effects of man-made chemicals on our health. I decided to develop a computational approach to objectively compare sensitivity of all genes to all chemicals and identify the most vulnerable biological processes.

Unbiased approach

For our study, my research colleagues and I used data from the Comparative Toxicogenomic Database. The Comparative Toxicogenomic Database collects information from thousands of published studies on how chemicals change the activity of genes. Genes are sections of DNA that encode proteins which perform a broad range of functions in cells, from building tissues to metabolizing nutrients. When chemicals affect genes, that results in increased or decreased production of proteins.

Modern methods of molecular biology can detect changes in activity of all genes in the genome in response to a chemical insult. I developed an approach that overlays lists of altered genes from different studies to calculate how many times each gene was affected. The resulting numbers reflect sensitivities of genes to chemicals generally.

Using 2,169 studies on mice, rats, humans and their cells, my research group ranked the sensitivity of 17,338 genes to chemical exposures. These studies tested the impact of 1,239 diverse chemicals ranging from prescription drugs to environmental pollutants.

At the next step we ran tests to ensure that this sample of over 1,000 chemicals was large enough to reliably represent all classes of man-made chemicals people are exposed to. To do so, we measured sensitivity of genes for one half of this list and then for another to test if even a smaller number of chemicals can reliably identify sensitive genes. The results were encouraging – the values of gene sensitivities were almost identical in the two trials.

Cellular defense system responds to chemicals

Our cells are not completely helpless when exposed to chemical insults. In fact, they possess strategies for dealing with stress and damage induced by chemicals. Our data confirm that these safeguards become active in response to exposures.

This line of defense includes enzymes that eliminate toxic chemicals, alleviate oxidative stress (the accumulation of reactive radicals in cells), repair damaged DNA and proteins, and identify highly damaged cells to trigger their death and prevent them from turning cancerous.

All molecular pathways are sensitive to chemicals

Overall we found that almost every known pathway may be affected by chemicals. That finding has significant implications for regulatory toxicology.

With ever-increasing numbers of man-made chemicals, society needs to develop rapid and cost-efficient methods of toxicity testing.

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One important question that remains unanswered is what pathways should be covered by testing to ensure that regulators do not approve chemicals that harm or disrupt critical molecular circuits. 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 for metabolic health, immune system, development and aging.The Conversation

Alexander Suvorov, Assistant Professor, University of Massachusetts Amherst

This article is republished from The Conversation under a Creative Commons license. Read the original article.

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