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Radical Research
It reads like a good mystery novel. The villain changes his identity and strikes quickly and viciously, causing irrevocable damage. He then disappears, leaving little evidence to find this dastardly culprit or to prevent his striking again.
Carl Bernofsky, research professor of biochemistry, is Sherlock Holmes in this mysterious tale. The environmental pollutant
- 1,1,2-trichloroethylene - is the elusive villain. A solvent used widely in the military and by industry to clean metal parts,
trichloroethylene is a frequent environmental contaminant of ground and surface water and is among the 10 most cited chemicals at
hazardous waste sites, according to government reports and scientific studies.
"There is a lot of this environmental pollutant around," Bernofsky says. "From waste sites, it percolates into the ground and into ground water. No one knows just how toxic it is to humans, but, in animals, it has been shown to be cancerous."
Bernofsky says studies have demonstrated that trichloroethylene causes lung, liver and testicular tumors in rodents, but little is known about the mechanism by which the compound can cause cancer. With a two-year, $250,932 grant from the Air Force Office of Scientific Research, he hopes to show how and why trichloroethylene is toxic in experimental animals.
His hypothesis is that free radicals are involved.
"Free radicals are compounds with a free electron on them that makes them very unstable and highly reactive," Bernofsky says. "You can't really get a handle on them. They're not like stable compounds that you can isolate and study. Trying to trap them is like trying to catch a bullet that's flying through the air. You know that the bullet has been there because you can see the target that it hits has been damaged. Free radicals act in the same way."
Bernofsky thinks that dangerous free radicals are formed as the liver breaks down the trichloroethylene into a variety of metabolites, including dichloroacetic acid and trichloroacetic acid.
"What our research is going to try and do is to show that these compounds are converted in the liver to free radicals," he says. "This free radical can combine with DNA to form an adduct. When it latches on to DNA, it can be mutagenic or carcinogenic. If it latches on to a protein or lipid, that can be merely toxic to the cell."
"The radicals form so quickly and disappear so quickly that you never see them," he says.
Bernofsky will use a machine called an electron paramagnetic resonance (EPR) spectrometer and a technique called "spin trapping" to look for free radicals. In 1992, Bernofsky received a Louisiana State Board of Regents grant to purchase a $250,000 EPR machine, which "does only one thing. It detects the presence of a free electron. But there is no other way to detect the presence of a free electron other than by using this piece of equipment," he says.
If he finds these radicals, he will use a radioactive label to study whether they connect to proteins, lipids and nucleic acids to form an adduct. If a nucleic-acid adduct forms, he will attempt to isolate enough of the material to analyze its structure using mass spectroscopy. Because nucleic acids are the building blocks of DNA, studying the structure of this adduct could help researchers understand the carcinogenic nature of the original trichloroethylene compound.
Bernofsky says this study is his first foray into research that applies the concept of free radicals to an environmental concern. Other Tulane research involving free radicals includes studies on nitric oxide; cardiac, brain and kidney disease; and inflammatory diseases. Free radicals can also form when blood and oxygen are cut off from an organ and later readmitted, Bernofsky says, and are a concern during transplant operations.
The fleeting and ephemeral nature of free radicals makes researching them a bit esoteric, Bernofsky says.
"This is not very mainstream work," he says.
- Judith Zwolak
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