UMass Amherst research compares sensitivity of all genes to chemical exposure

October 29, 2020

A University of Massachusetts Amherst environmental health scientist has used an unprecedented objective approach to identify which molecular mechanisms in mammals are the most sensitive to chemical exposures.

The study, published in the journal Chemosphere, advances the understanding of the interaction of chemicals, both pollutants and pharmaceuticals, on gene expression and the impact on human health.

"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," says lead author Alexander Suvorov, associate professor in the School of Public Health and Health Sciences.

The study identified genes and molecular pathways most sensitive to chemical exposures, including mechanisms involving aging, lipid metabolism and autoimmune disease. "These findings for the first time prove that current epidemics in metabolic and autoimmune disorders may be partly due to a very broad range of chemical exposures," Suvorov says.

To carry out their analysis, Suvorov and five students - undergraduates Victoria Salemme, Joseph McGaunn and Menna Teffera, and graduate students Anthony Poluyanoff and Saira Amir - extracted data on chemical-gene interactions from the Comparative Toxicogenomics Database, which includes human, rat and mouse genes.

The UMass Amherst team created a database of 591,084 chemical-gene interactions reported in 2,169 studies that used high-throughput gene expression analysis, which means they looked at multiple genes. Low-throughout analysis focuses only on a single gene.

"In the recent past, everything that we knew about molecular mechanisms affected by chemicals was coming from low-throughput experiments," Suvorov says, which led toxicology researchers to focus on those already identified genes, rather than looking for chemical sensitivity among a fuller range of genes.

"I wanted to find some approach that would tell us in a completely unbiased way which mechanisms are sensitive and which are not. I wondered if we were missing a significant toxic response just because no one ever looked for it," Suvorov says. "By overlaying many high-throughput studies, we can see changes in the expression of all genes all at once. And that is unbiased because we are not cherry-picking any particular molecular mechanisms."

The interactions analyzed encompassed 17,338 unique genes and 1,239 unique chemicals. The researchers split their database of chemicals into two parts - pharmaceutical chemicals, which are designed to target known molecular cascades; and other chemicals such as industrial, agricultural, cosmetics and pollutants. When the sensitivity of genes to pharmaceutical chemicals was compared to the sensitivity of genes to the other chemicals, the results were the same. "That proves that when analysis is done on really big numbers of chemicals, their composition does not matter," Suvorov says.

The study confirmed the molecular mechanisms that were previously recognized as being sensitive to chemical exposure, such as oxidative stress. The study's new findings that the pathways involving aging, lipid metabolism and autoimmune disease are also highly sensitive suggest that chemical exposures may have a role in such conditions as diabetes, fatty liver disease, lupus and rheumatoid arthritis, among others.

"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."

University of Massachusetts Amherst

Related Public Health Articles from Brightsurf:

COVID-19 and the decolonization of Indigenous public health
Indigenous self-determination, leadership and knowledge have helped protect Indigenous communities in Canada during the coronavirus disease 2019 (COVID-19) pandemic, and these principles should be incorporated into public health in future, argue the authors of a commentary in CMAJ (Canadian Medical Association Journal)

Public health consequences of policing homelessness
In a new study examining homelessness, researchers find that policy such a lifestyle has massive public health implications, making sleeping on the street even MORE unhealthy.

Electronic health information exchange improves public health disease reporting
Disease tracking is an important area of focus for health departments in the midst of the COVID-19 pandemic.

Pandemic likely to cause long-term health problems, Yale School of Public Health finds
The coronavirus pandemic's life-altering effects are likely to result in lasting physical and mental health consequences for many people--particularly those from vulnerable populations--a new study led by the Yale School of Public Health finds.

The Lancet Public Health: US modelling study estimates impact of school closures for COVID-19 on US health-care workforce and associated mortality
US policymakers considering physical distancing measures to slow the spread of COVID-19 face a difficult trade-off between closing schools to reduce transmission and new cases, and potential health-care worker absenteeism due to additional childcare needs that could ultimately increase mortality from COVID-19, according to new modelling research published in The Lancet Public Health journal.

The Lancet Public Health: Access to identification documents reflecting gender identity may improve trans mental health
Results from a survey of over 20,000 American trans adults suggest that having access to identification documents which reflect their identified gender helps to improve their mental health and may reduce suicidal thoughts, according to a study published in The Lancet Public Health journal.

The Lancet Public Health: Study estimates mental health impact of welfare reform, Universal Credit, in Great Britain
The 2013 Universal Credit welfare reform appears to have led to an increase in the prevalence of psychological distress among unemployed recipients, according to a nationally representative study following more than 52,000 working-age individuals from England, Wales, and Scotland over nine years between 2009-2018, published as part of an issue of The Lancet Public Health journal on income and health.

BU researchers: Pornography is not a 'public health crisis'
Researchers from the Boston University School of Public Health (BUSPH) have written an editorial in the American Journal of Public Health special February issue arguing against the claim that pornography is a public health crisis, and explaining why such a claim actually endangers the health of the public.

The Lancet Public Health: Ageism linked to poorer health in older people in England
Ageism may be linked with poorer health in older people in England, according to an observational study of over 7,500 people aged over 50 published in The Lancet Public Health journal.

Study: Public transportation use linked to better public health
Promoting robust public transportation systems may come with a bonus for public health -- lower obesity rates.

Read More: Public Health News and Public Health Current Events is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to