Forever common chemicals may trigger cancer cell spread: ScienceAlert

Forever common chemicals may trigger cancer cell spread: ScienceAlert

When colorectal cancer cells are exposed to two different types of “forever chemicals” in the laboratory, the chemicals are likely to accelerate cancer progression, a new study suggests.

A new study analyzed exposure levels similar to those found in firefighters and other people who regularly handle perfluoroalkyl and polyfluoroalkyl substances (PFAS).

PFAS levels in firefighters’ blood tend to be higher than those of the general population due to their frequent exposure to firefighting foam, which contains PFAS chemicals for its flame-retardant properties.

Firefighters are more likely than the general population to develop and die from a variety of cancers that include colorectal cancer. Environmental factors are thought to be linked to about 80 percent of CRC cases.

In the new research, exposure to PFAS in the laboratory stimulated CRC cells to migrate to new sites, suggesting a possible role in the spread of cancer (metastasis) in living organisms.

“It doesn’t prove metastasis, but they have increased mobility, which is a characteristic of metastasis,” says Carolyn Johnson, an epidemiologist at Yale University.

PFAS are man-made chemicals based on carbon-fluorine bonds, and as the nickname “forever chemicals” suggests, these bonds are very strong and resistant to degradation, making PFAS commonly used in many types of products. Unfortunately, it also allows them to remain in the environment for years in ever-increasing concentrations.

“PFAS constitute a prevalent class of persistent organic pollutants that are of increasing public concern worldwide,” says co-first author and physiologist Ji Cheng of Yale University.

“They have been frequently detected in the environment, such as drinking water, indoor dust, cleaning products, and paints.”

Many of these “forever chemicals” are still found in everyday items, although the dangers of PFAS are largely unclear – in part due to the many different compounds found in them.

Research has shown that these long-lasting chemicals spread throughout the environment, and that exposure to high levels is associated with adverse health effects in humans and animals.

Perfluorooctanoic acid (PFOA), a widely used PFAS, was classified as carcinogenic to humans by the International Agency for Research on Cancer in November 2023, and perfluorooctanesulfonic acid (PFOS), another common PFAS, was classified as likely. Carcinogenic to humans.

To study how it affects aggressive CRC, Cheng, Johnson and colleagues used CRC cells and lab-grown metabolomics — a process that measures levels of metabolites, thousands of small molecules such as amino acids, lipids, and proteins.

“We look at patterns that occur within an at-risk group of people or a sick group of people, and then we try to generate a hypothesis about why someone might get a disease or develop a disease,” Johnson says.

“Metabolomics is one of the only tools where you can measure environmental exposure in the same sample as the biological effect.”

Two types of CRC cells, shaped into balls called spheroids, were used in the experiments. The wild-type KRAS gene was present in one species, while the other had a common mutation in the KRAS gene, which is associated with particularly aggressive CRC.

When exposed to PFOS and PFOA, the cells showed increased motility and a greater tendency to spread. In a different test of CRC cells grown in a flat layer, a line was scratched down the middle to divide them. When chemicals were introduced, the cells grew and moved toward each other again.

To go deeper, the researchers examined the effects of chemicals on cell metabolism. Exposure to PFAS altered various metabolites important for cell function, such as amino acids and fatty acids, as well as signaling proteins associated with metastasis.

Substances that are normally anti-inflammatory and cancer-protective in CRC cells were reduced after exposure as well. Some of the differences were more pronounced in the mutant cells, which could mean that cancers carrying this mutation may be more likely to spread when exposed to PFAS.

These in vitro findings suggest that exposure to high levels of PFOS and PFOA can increase the risk of CRC spread in real-life settings. The team says this is important information for those who work in jobs where they are potentially exposed to high levels, and monitoring these chemicals is key to protecting their health, as is the case for future clinical studies.

“Many in vitro studies cannot be translated to humans, but I think understanding the mechanisms of how they actually affect cancer cell growth is important first,” Johnson explains.

The study was published in Environmental science and technology.

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