Space radiation sparks: A biological cascade of cancer

Deep space travel comes with a huge potential downside—radiation exposure that can kill an astronaut either quickly or slowly over time if not managed correctly. But what exactly does that mean, and is there any way to handle it other than sticking more and more protective layers between the squishy biological systems inside a spacecraft and the radiative void of deep space?

A new paper from researchers at Oklahoma State University and the University of Texas Health Science Center aims to answer both questions. While the sources of radiation they identify are complex, they also offer some potential solutions.

Scientists have long known that one of the main causes of cancer in deep space travelers (and even airline pilots) is galactic cosmic rays (GCRs). These are high-energy atomic nuclei that have been stripped of their electrons and accelerated by massive shock waves from supernovae. But they are typically stopped by the protective blanket of Earth’s atmosphere before they can reach anyone on the ground.

Astronauts in space are not so lucky, as they are subjected to high levels of GCRs, including the most dangerous kind—high-atomic-number, high-energy ions known as HZE ions, such as iron nuclei (Fe-56). Iron ions are much more destructive than even X-rays, leaving a dense trail of ionization that literally rips through DNA strands and, with enough exposure, will almost certainly cause cancer.

However, they are relatively rare. For a typical three-year round trip to Mars, calculations based on data from Curiosity’s journey there suggest that only about 3% of an astronaut’s cells would take a direct hit from an iron ion. That doesn’t sound terrible, given that it means 97% of a person’s cells would avoid a direct hit. But flight surgeons are alarmed about what they call the radiation-induced bystander effect.

To showcase this danger, the researchers gathered groups of human aortic endothelial cells—the kind that line the walls of blood vessels—and subjected them to Fe-56 ion beams at Brookhaven National Laboratory’s NASA Space Radiation Laboratory. In such conditions, it becomes readily apparent that cells directly hit by iron ions can’t simply repair themselves or even die off. Instead, they start an inflammatory signaling cascade.

After a cell is hit with an iron ion, it activates a transcription factor called NF-κB, which is crucial for inflammation and cellular defense. It also turns on the production of another important inflammatory messenger molecule called tumor necrosis factor-alpha (TNF-α).

Some of this molecule attaches back to the surface of the cell that secreted it in what is called an autocrine loop. This prompts more NF-κB activation and reinforces the inflammatory distress signaling loop for upward of three days.

But some of those TNF-α molecules also wash over neighboring cells and cause havoc there. To showcase this, the researchers put some of the irradiated endothelial cells into a porous mesh hovering just above a group of normal epithelial cells—the kind that line lungs. The two lines of cells didn’t physically touch and were only interconnected through a liquid medium that chemical signals could travel through.

Despite the physical disconnect, nearby cells were heavily affected by the TNF-α coming from their irradiated neighbors. They suffered from massive free radical spikes, with a notable increase in double-stranded DNA breaks.

The incoming TNF-α also bypassed a normal biological “kill switch” that would prevent a cell’s harmful mutations from spreading by switching on several anti-death genes and activating a growth signal. In other words, the TNF-α disabled the exact mechanisms a cell would typically use to stop itself from becoming cancerous.

To further prove their point, the researchers turned to mouse models. They implanted some noncancerous epithelial cells that had simply been in the presence of the irradiated endothelial cells into mice and watched as those exact cells grew substantial tumors. In other words, cells that had never been directly hit by a GCR had begun to grow tumors simply because they had been around other cells that had.

In yet another step up the biological testing chain, the researchers also looked at data from the Space Omics and Medical Atlas experiment, which took a series of blood samples and tissue biopsies from astronauts on the SpaceX Inspiration4 mission in 2021. They found systemic spikes in TNF-α, as well as heightened activity of anti-death genes that were triggered as part of the radiation cascade. In other words, these effects weren’t just some laboratory quirk—they seem to be taking place in real astronauts too.

So, this has all sounded like bad news. But there is a silver lining—if we know the chemical signaling pathway for this breakdown of cell function, we can introduce countermeasures. The researchers did manage to break the cascade by inhibiting the TNF-α receptor and halting NF-κB activation, allowing cells to avoid the cancerous transformations at the end of the chemical signaling path.

Combining those chemical interventions with advanced shielding techniques, such as water walls and hydrogen-rich polymers like polystyrene, could drastically limit the occurrence of cancer in future deep space travelers. But it will take a lot more research to prove our protective techniques are up to the task. Before we start sending lots of humans out into the void crisscrossed by GCRs, it’s worth taking a closer look at how we can save them from these particularly dangerous particles.

Who’s behind this story?

Sadie Harley

BSc Life Sciences & Ecology. Microbiology lab background with pharmaceutical news experience in oil, gas, and renewable industries.

Full profile →

Andrew Zinin

Master’s in physics with research experience. Long-time science news enthusiast. Plays key role in Science X’s editorial success.

Full profile →