Toxic “forever chemicals” are altering human liver function at a fundamental level by triggering both fat accumulation and cancer-linked cell damage, a new study has found.
Several of these compounds, also known as perfluoroalkyl and polyfluoroalkyl substances (PFAS), interrupt liver cell signaling and immune functions but do so via unique mechanisms, scientists observed in the study, published in Environment International.
The disruptions were also sex-specific — affecting donor liver cells of males and females in different ways, according to the research.
“These chemicals change our bodies,” said senior author Ana Maretti-Mira, an assistant professor of research medicine at the University of Southern California’s Keck School of Medicine, in a statement.
Notorious for their ability to persist both in the human body and in the environment, PFAS are present in numerous household products, as well as in certain types of firefighting foam.
While PFAS have been linked to multiple kinds of cancer and other serious illnesses including liver disease, it remains unclear exactly how they cause damage to the liver.
Taking one step closer toward solving that mystery, Maretti-Mira and her colleagues exposed human liver cells to four types of PFAS in the lab and then measured shifts in gene expression and fat buildup.
Specifically, they used liver “spheroids,” miniature models of the liver constructed from the cells of 10 human donors: five males and fie females. In the laboratory, they then exposed the spheroids to four types of PFAS that are commonly found at high levels in human blood: PFOA, PFHxS, PFOS and PFNA.
After a week of exposure, the scientists separated the spheroids into individual cells to analyze gene expression and to measure fat accumulation. Although all four types of PFAS caused interference, their precise effects varied, the authors discovered.
Both PFOA and PFHxS caused a rise in fat accumulation: PFOA by causing cells to create more fat and PFHxS by prompting them to retain it, according to the study.
“These are different cellular processes with the same result,” Maretti-Mira said.
While those results might not be favorable, Maretti-Mira stressed the value in understanding these mechanisms, as that knowledge “may ultimately allow us to design targeted interventions.”
Meanwhile, PFOS and PFNA triggered cancer-related changes, with PFNA exhibiting more pronounced effects: a surge in cellular pathway activity linked to inflammation, oxidative stress and DNA repair, per the research.
Of all cells exposed to PFNA, 61.3 percent underwent gene changes associated with cancer, the authors found.
As far as the gender variances are concerned, the scientists observed stronger effects of PFOA on female liver cells and more robust impacts of PFOS on male cells.
This additional information, they explained, could also help guide different treatment strategies.
Some drugs that regulate how the liver processes fat, the authors noted, are already approved by the Food and Drug Administration and could be tested for treating PFAS-induced liver damage.
But at the same time, the scientists stressed the importance of taking individual action to limit PFAS exposure, by making personal choices such as drinking filtered water and avoiding nonstick pans.
“These chemicals change our bodies and we cannot wait for government regulations to take effect,” Maretti-Mira said. “Be aware of how you can be exposed and try to limit that exposure.”
