Agricultural Fungicide Could Cause Irreversible Immune System Damage

Contact: Charmayne Marsh 202-872-4445 in Washington

April 4--11, 2002, in Orlando407-685-8070

EMBARGOED FOR RELEASE: Monday, April 8, 8:00 p.m., Eastern Time

Agricultural fungicide could cause irreversible immune system damage

ORLANDO, Fla., April 8 -- Natural 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 front-line 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, Ph.D., 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, Ph.D., 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.

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The poster on this research, ENVR 166, will be presented at 8:00 p.m., Monday, April 8, at the Convention Center, Hall C, during Sci-Mix, and again at 6:00 p.m., Wednesday, April 10, at the Convention Center, Hall C, during a general poster session.

Margaret Whalen, Ph.D., is an assistant professor of chemistry at Tennessee State University in Nashville.

Sharnise Wilson is a chemistry major in her junior year at Tennessee State University in Nashville.

Bommanna Loganathan, Ph.D., is an assistant professor in the Department of Chemistry at Murray State University in Murray, Ky.

-- Marvin Coyner

#13180 Released 04/8/2002

Embargoed: Monday, April 8, 8:00 p.m., Eastern TimeENVR 166 [500841]

Brief triphenyltin exposure causes irreversible inhibition of the cytotoxic function of human natural killer cellsSharnise Wilson1, Bommanna G. Loganathan2, and Margaret M. Whalen1. (1) Department of Chemistry, Tennessee State University, 3500 John A. Merritt Blvd., Nashville, TN 37209, Fax: 615-963-5326, [email protected], Phone: 615-963-5247, (2) Department of Chemistry, Murray State University

Phenyltin (PT) contamination has been reported in water, sediment, and fish. Triphenyltin (TPT) has been implicated in a wide spectrum of toxic effects in exposed animals, including increased tumor formation. Human exposure to TPT might come from occupational exposure as well as consumption of contaminated food. Natural Killer cells are a primary immune defense against tumor and virally infected cells. Previously, we reported that exposure to TPT significantly inhibited the tumor killing capacity of human NK cells. In this study we examine whether the inhibition of NK-cell cytotoxicity induced by a 1 h exposure to TPT is reversible, when the cells are allowed to recover in TPT-free media for up to 6 days. The results revealed that exposure to 750 nM TPT for 1h caused a 57% decrease in NK-cytotoxic function. However, if the cells were allowed to incubate in TBT-free media for 24 h there was an 84% inhibition of NK cytotoxicity. There was no significant recovery of NK-cytotoxic function when the lymphocytes were allowed to incubate in TPT-free media for up to 6 days. The results indicated that short-term exposure to TPT caused persistent negative effects on NK-cell ability to kill cancer cells.

Embargoed For Release: Monday, April 8, 8:00 p.m., Eastern Time

Non-Technical Summary

ENVR 166

Division: Division of Environmental ChemistryAbstract ID Number: 500841Title: Brief triphenyltin exposure causes irreversible inhibition of the cytotoxic function of human natural killer cells

Dear Sharnise Wilson,The ACS Office of Communications is currently reviewing abstracts for the 223rd ACS National Meeting--Orlando, Florida (April 7-11, 2002) in Orlando, for possible topics of interest to the news media. To help us better understand your poster/paper, please provide the following summary information regarding your presentation as quickly as possible, preferably within one week of receipt.

* Briefly explain in lay language what you have done, why it is significant and its implications, particularly to the general public.

Using standard methods we have demonstrated for the first time that a brief (1 h) exposure of human immune system cells (natural killer lymphocytes)to triphenyltin (TPT) causes a loss of the cellular function (ability to kill tumor cells) that is not reversed when the TPT is removed.

These results indicate that brief exposures to TPT can cause persistent suppression of human immune system function.

The fact that TPT causes persistent negative effects on immune system function has implications for what constitutes a safe duration and level of exposure to this compound.

* How new is this work and how does it differ from that of others who may be doing similar research?

To our knowledge there are no similar studies of the persistent inhibitory effects of TPT on human natural killer lymphocytes.

* Indicate if the material in your presentation (or similar research) has received prior media coverage and, if so, which publications or broadcast stations might have reported it.

This work has not received prior media coverage.

* Corresponding author's name and business title or position: Margaret M. Whalen, Ph. D.Assistant Professor

* Work department:Chemistry

* Business address including organization:Tennessee State University 3500 John Merritt Blvd.Nashville, TN 37209

* Telephone:615-963-5247

* Fax:615-963-5326

* E-mail address:[email protected]

* Name and contact information for corresponding author's organization's public relations person:Phyllis Qualls-Brooks ph:615-963-5331

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