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Exposure to steer may cause epigenetic modifications even at comparatively low ranges

Publicado em 17 maio 2021

A gaggle of Brazilian and Portuguese researchers noticed a correlation between the presence of lead within the organism and a microRNA (miRNA) that may very well be related to the mechanisms that regulate DNA methylation, a physiological course of required to manage gene expression and be certain that genes perform correctly.

The alterations have been detected in blood cells from staff in automotive battery vegetation, which use lead as a uncooked materials. Curiously, lead ranges in blood samples from 85 volunteers—averaging 20 micrograms per deciliter of blood (20 µg/dl)—have been decrease than the appropriate ceiling outlined in Brazilian regulation (60 µg/dl).

The examine was supported by FAPESP and reported in an article printed in Frontiers in Genetics. The authors are affiliated with the Federal University of São Paulo (UNIFESP), the Federal University of the ABC (UFABC), Anhembi Morumbi University, and the University of São Paulo (USP) in Brazil, and the New University of Lisbon (UNL) in Portugal. The examine was a part of a mission funded by FAPESP.

“What all the studies conducted to date suggest, albeit incipiently, is that low-level exposure to lead isn’t necessarily associated with a lack of adverse effects but may correlate with molecular events that precede the events that are well-established in the literature as deriving from chronic lead poisoning, such as neurological and hematological problems,” stated Gustavo Rafael Mazzaron Barcelos, final creator of the article. Barcelos is a professor at UNIFESP’s Institute of Health and Society (ISS) in Santos, São Paulo state.

Although low doses didn’t correlate straight with health problems, he added, the DNA alterations ought to function a warning. “These levels cannot be considered safe. It would be great if lead exposure levels could be minimal, but a whole industrial system depends on production of lead. We need good public policy to minimize exposure, which we’ve been observing systematically in Brazil for decades,” Barcelos stated.

In Brazil, any lead publicity exceeding 60 µg/dl should be reported to the SUS, the nationwide well being service, and the social safety authorities. In China, analysis has proven that native staff have increased blood lead levels, averaging round 40 µg/dl.

“We analyzed DNA methylation, one of the epigenetic changes that occur mainly in promoter regions, which control gene functions. When methylation in these regions undergoes such changes, protein synthesis may become dysregulated, potentially causing problems. There’s evidence that lead exposure can inhibit DMNT1, the enzyme responsible for controlling DNA methylation. In the samples we analyzed, we found an abundance of miR-148a, a miRNA that targets the gene for DMNT1,” stated Marilia Ladeira de Araújo, first creator of the article. The examine was a part of her Ph.D. analysis at ISS-UNIFESP. She carried out a part of the evaluation whereas working as a analysis intern at UNL’s Medical School with a scholarship from FAPESP.


In a earlier examine, the group had detected an total lower in DNA methylation in the identical employee cohort, utilizing samples taken at vegetation within the state of Paraná. Reported within the Journal of Toxicology and Environmental Health, Part A, the examine was a part of the grasp’s analysis of Paula Pícoli Devóz on the University of São Paulo’s Ribeirão Preto School of Pharmaceutical Sciences (FCFRP-USP). Devóz can also be a co-author of the newest printed examine.

The researchers then determined to search for biomarkers of decreased DNA methylation, figuring out a number of miRNAs that may very well be related to this occasion. They noticed a major improve in miR-148a, famous within the literature as being related to DNA injury, inflammatory processes, and oxidative stress, all of which can correlate with the event of multifactor pathologies reminiscent of neurodegenerative illnesses and most cancers, for instance.

“The advantage of using miR-148a as a biomarker of epigenetic disturbances induced by lead exposure is that these alterations in its expression may precede various cellular disorders, such as oxidative stress and cell death,” Barcelos stated. “We don’t yet know whether a decrease in DNA methylation has adverse effects. We analyzed the overall status of this parameter in DNA as a whole, but we now know it’s a potential biomarker of this condition.”

As quickly because the pandemic is over, he plans to proceed the analysis by amassing extra samples from the identical cohort over a comparatively lengthy interval to see if the results of low-level publicity persist and the way the organism can adapt to it.

More info:
Marília Ladeira de Araújo et al, Association Between miR-148a and DNA Methylation Profile in Individuals Exposed to Lead (Pb), Frontiers in Genetics (2021). DOI: 10.3389/fgene.2021.620744

Exposure to steer may cause epigenetic modifications even at comparatively low ranges (2021, May 17)
retrieved 17 May 2021

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