Russian troops exposed to radiation, Chernobyl experts say

Thousands of enemy tanks and troops rumbled into Chernobyl during Russias invasion of Ukraine churning up highly contaminated soil.

Scott L. Hall, USA TODAY

Scientists in Tennessee are developing a promising drug they desperately hope will never be used.

Its a treatment that could rescue people from gastrointestinal acute radiation syndrome. In blunt terms, radiation poisoning.

"We were so damn lucky to find this mechanism that nature invented for us," said Dr. Gabor Tigyi,a cell biologist and cancer researcher at the University of Tennessee Health Science Center in Memphis. "We made a drug to harness it. .. It took about 20 years to figure out what we had in hand."

There is no drug on the market for the treatment of this illness. It's a weakness in our country's preparedness for nuclear accidents and attacks.

The drug is important locally, too. Much of the nations nuclear waste is processed in Tennessee. The state is home to many legacy nuclear sites, some of which date back to the World War II Manhattan Project.

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When the human body is exposed to radiation, high-energy particles penetrate cells and tissues to damage our DNA and cellular machinery. DNA damage is the reason why radiation exposure can induce cancers. Not all DNA damage repair occurs without error, and those errors can induce mutations that favor tumors.

When the body is exposed to very high levels of radiation for a brief period of time the kind of exposure that can happen in a nuclear accident the danger isnt necessarily cancer but loss of function in organs and tissues. Each tissue has different tolerances for radiation doses.

Two of the most sensitive tissues are bone marrow and intestinal tissue. Bone marrow is the nursery of red and white blood cells. Stem cells in the bone marrow constantly grow and divide to replace blood cells that expire.

"The lymphocytes in the blood and bone marrow, those are exquisitely sensitive," said Carol Iddins, director of theRadiation Emergency Assistance Center/Training Site in Oak Ridge. "They are arguably the most sensitive cells in our bodies so they're going to drop faster and harder."

But bone marrow damage from radiation already has treatments, and they are effective. Those drugs were developed for cancer patients undergoing radiation therapy.

"That was a low-hanging fruit, really," said Andrea DeCarlo-Cohen, director of the, Radiation and Nuclear Countermeasures Program at the National Institute for Allergy and Infectious Diseases. Because bone marrow complications kill much faster than other radiation complications, the drugs were prioritized, she said.

But no treatment existed for gastrointestinal cells.

"It's a much more complex injury," DeCarlo-Cohen said. "The stem cell biology of the GI tract is behind. ...It's just a much more complex structure."

The intestine is lined with a single layer of rapidly-diving cells. These cells grow upward into wavy, hair-like structures called villi. The stem cells and youngest cells are at the bottom. As cells age, they are pushed up the villi until they are shed into the intestine. Each intestinal cell lives for about four or five days before being shed.

That kind of cell turnover requires active adult stem cells. The intestine is full of them, constantly growing and dividing. When the intestine is hit by a high dose of radiation, it can damage the stem cells, causing them to self-destruct.

One of the ways the body prevents most cancersis a cellular self-destruct mechanism called apoptosis.

Tigyi'sdrug stimulates the DNA repair mechanism and slows down apoptosis. This buys some time for the intestinal stem cells to save themselves from radiation damage.

In tests on mice and monkeys, Tigyi's drug improved the survival rate after radiation exposure.

Tigyioriginally stumbled onto this mechanism while looking at platelets, the cell fragments your body uses to form blood clots. He found a short-lived signaling molecule, LPA,associated with wound repair.

"Our compound is modeled after this natural compound,"Tigyi said. "It promotes these mechanisms that lead to survival, regeneration and radiation protection."

If you can interrupt the self-destruct process long enough for the cells natural DNA repair mechanism to kick in, then you can potentially savestem cells and prevent catastrophic damage.

"The fundamental issue is enhancing DNA repair," Tigyi said. "Your cells are programmed such that if DNA damage is not repaired, the cell undergoes apoptosis and dies."

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Dr. Shannon McCool was brought in to shepherd the drug process through FDA approvals. McCool is a graduate of UT's Health Science Center who has worked for large pharmaceutical operations like Eli Lilly and has experience navigating the regulatory landscape.

In 2000, the duo founded RxBio, a pharmaceutical company in Johnson City, toensure the drug was approved for treatment. The research wasin the final rounds of safety testing when the COVID-19 pandemic hit.

The pandemic didnt just make the research harder from a logistical standpoint.McCool said it becamedifficult to get funding.

"Nobody would give you the time of day," McCool said, referring to discussions with the Pentagon about defense-oriented medical funding."COVID-19 had sucked all the air out of the room."

A drug like this doesnt have to go through the standard FDA phased clinical trials because, of course, its not ethical to irradiate human beings.But itdoes have to go through extensive safety testing in large animal model systems. Thatcan be expensive.

Nowthere is potential space for the drug to get additional funding. Tigyi hopes that working with the Tennessee congressional delegation will help secure enough funding to begin passing the FDA's safety standards.

"We've been barely staying alive for the last several years," McCool said. "We estimate that we need $35 million, plus another 50-100 million on top of that to get everything done that we estimate the FDA will want us to do."

In an earlier version of this storyDr. Gabor Tigyi's name wasmisspelled. The error has been corrected in this version.

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'We were so damn lucky to find this': Tennesseans close to developing radiation exposure drug - Knoxville News Sentinel