BOULDER, Colo. — We’re all made up of incredible tiny cells that work together to allow our bodies to function. Sometimes, however, cells can go rogue and start behaving in unhealthy ways that lead to serious diseases like cancer. Imagine if there was a way to simply look at the molecular makeup of cells and be able to tell whether they are operating normally or abnormally without any invasive testing. Well, scientists may have found a clever new method to do just that — uncovering the atomic fingerprints of cancer.
In a fascinating study published in the journal PNAS, researchers discovered that the levels of certain isotopes (different versions of the same element that have slightly varying weights) in the fatty acids of cells can reveal important clues about the cells’ inner metabolic workings. More specifically, the ratio of heavy hydrogen (deuterium) to normal hydrogen in fatty acids seems to act as a natural fingerprint, revealing whether cells are respiring normally or fermenting in an unhealthy way, as cancer cells do.
It all comes down to a crucial molecule called NADPH that acts as cells’ main supplier of energizing electrons for important biochemical reactions. The way cells produce NADPH depends on whether they are respiring by burning oxygen like a healthy cell or fermenting and rapidly proliferating like a cancerous cell. During normal respiration, cells produce more NADPH from an enzyme pathway that leaves a unique deuterium-enriched signature in the fatty acids those NADPH molecules help synthesize.
By contrast, cancer cells forced to ferment sugars for rapid growth rely more heavily on different NADPH-producing enzymes that create a deuterium-depleted pattern in the fatty acids they help generate. Simply put, by measuring the deuterium levels of extracted fatty acids, the researchers could tell whether the cells were healthy and respiring — or cancerous and fermenting.
“This study adds a whole new layer to medicine, giving us the chance to look at cancer at the atomic level,” says Ashley Maloney, a research associate in the Department of Geological Sciences at the University of Colorado Boulder, in a media release.
The scientists made this discovery by first running detailed experiments with ordinary baker’s yeast cells, a powerhouse model organism for studying cellular metabolism. Growing the yeast in special reactors and tightly controlling nutrient levels could force the yeast cells to either ferment sugar or burn an alternate food source like glycerol, mimicking the metabolisms of cancer and healthy cells, respectively.
When they carefully measured the deuterium/hydrogen ratios in the fatty acids extracted from yeast grown under fermenting versus respiring conditions, there was a massive difference – over 550 per million! Fermenting yeast had fat molecules depleted in deuterium, while the respiring yeast showed extreme deuterium enrichments. The degree of enrichment or depletion varied further with the rate of yeast growth, reflecting how cells reshuffle their NADPH-producing enzyme toolkit depending on metabolic demands.
To see if their yeast findings could translate to real life, the team also tested fatty acid deuterium levels in cancerous mouse liver cells and healthy mouse liver cells grown in lab dishes. Sure enough, the deuterium fingerprint matched that of the yeast experiments, with fatty acids from the fast-growing, fermenting cancer cells showing deuterium depletion compared to the normal, respiring liver cells.
“When we started the study, I thought, ‘Ooh, we have a chance to see something cool,’” Maloney says. “It ended up creating a huge signal, which I didn’t expect.”
While still an early result requiring further investigation across different cell types, the finding that such a simple deuterium isotope measurement can potentially distinguish healthy and diseased cells is game-changing. It points to new ways we could easily and non-invasively screen for abnormal cellular metabolism, a key hallmark of not just cancer but many other serious conditions, too.
Rather than having to surgically sample cells and tissues for complex tests, this deuterium tracer could allow screening from biofluid samples like blood or urine whenever cells shed fatty acid molecules. It’s the ultimate mobile health monitoring – every biofluid sample would contain clues about whether cells are functioning properly just from their fatty acid deuterium levels.
Of course, much more research is still necessary to validate and refine this new isotope approach across many different cells, organisms, and diseases. But the core discovery is revolutionary – that hydrogen isotopes hold remarkable power for naturally fingerprinting healthy and diseased metabolism.
StudyFinds Editor Chris Melore contributed to this report.