Agricultural fungicide could cause irreversible immune system damage

provided by American Chemical Society

atural killer cells are like the Marines of our immune system: they have the capability to defend us against a lot of different threats. But researchers have uncovered a potential counter-threat to this frontline protection. Our body's natural killer cells could be rendered irreversibly powerless to guard against invading tumors and viral onslaughts after only a brief exposure to a compound found in some agricultural pesticides and fungicides. The findings were presented at the 223rd national meeting of the American Chemical Society, the world's largest scientific society.

    Triphenyltin (TPT) is a compound used in fungicides to protect pecan, potato and sugar beet crops and in pesticides to guard against Colorado potato beetles. In tests at Tennessee State University in Nashville, researchers have found an apparent irreversible inhibition of natural killer cell function after as little as a one-hour exposure to TPT.

    The laboratory tests were the first to ever examine TPT specifically in human natural killer cells, according to chemistry professor Margaret Whalen, PhD, who oversaw the work. Most other studies involved animal cell lines, she said during a telephone interview. It's also the first time the irreversible effect has been shown, she added.

    The findings were presented by one of the contributing researchers, Sharnise Wilson, a chemistry major and one of Whalen's undergraduate students. “The results indicate that brief exposures to TPT can cause persistent suppression of human immune system function,” Whalen emphasized.

    Although Whalen thinks that most of the TPT levels that agricultural workers are exposed to in the field are probably below what her group tested in the lab, “It's hard to know what real-life levels for phenyltins are,” she noted. In the near future, Whalen, in collaboration with Bommanna Loganathan, PhD, of Murray State University in Kentucky, hopes to test blood samples of agricultural workers who have been exposed to TPT to see whether significant quantities of the compound can be measured in their blood.

    A type of lymphocyte cell found in the immune system, natural killer cells aggressively “fight a viral infection or destroy a cancer cell before other immune system cells recognize that they are there,” Whalen pointed out. “They are quite important.”

    A one-hour exposure to TPT “causes about a 50 percent to 60 percent loss of the tumor killing function of the natural killer cell,” according to Whalen. Even after the TPT is removed, the natural killer cells are unable to regain their strength, as evidenced by tests by Whalen's group with human leukemia cells.

    “Despite the fact that the compound is no longer there, they are still unable to kill the leukemia cell,” Whalen said. Whalen believes the findings “could explain to some extent why compounds like this seem to increase cancer risks.”

    The researchers are currently investigating whether interleukin-2 – a protein produced by other immune system cells – might help reverse the inhibitory effect of TPT. “It looks like it can to some extent,” according to Whalen, but she quickly points out that the study is still ongoing and there is no conclusive data.

    The research is primarily funded by the National Institutes of Health's Minority Biomedical Research Support (MBRS) program. Margaret Whalen, PhD, is an assistant professor of chemistry at Tennessee State University in Nashville.