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NTP Holds Biomarkers Workshop

By Robin Arnette
October 2006

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(Image courtesy of EHP)

The National Toxicology Program (NTP) sponsored a workshop titled "Biomarkers for Toxicology Studies" on September 20-21 in Rodbell Auditorium. The meeting brought together experts in lipid/carbohydrate metabolism, lung disorders and cardiac function to identify and evaluate biomarkers for inclusion in rodent toxicology studies. Adding new tests to the current battery of evaluations will make toxicological testing more precise and give investigators a better understanding of how environmental toxicants affect rodents and humans.

The workshop began with a welcome by NTP Interim Associate Director Allen Dearry, followed by a charge from the workshop chair, President of the Society of Toxicology James A. Popp of Stratoxon LLC. The morning session was dedicated to overview presentations about the NIEHS Exposure Biology Program, biomarker characterization and standard biomarkers currently in use in lipid/carbohydrate metabolism, lung and heart. During the afternoon session, the three groups participated in breakout sessions, with each group responsible for recommending new biomarkers that could provide valuable toxicological data. For background information the co-chairs, Gregory Travlos and June Dunnick of NIEHS, compiled lists of biomarkers for the three areas as a starting point for group discussions. Group findings were reported during the second day of the workshop.

Steven Kleeberger of NIEHS chaired the lung biomarker group and said that his group recommended that bronchoalveolar lavage analysis, enhanced histopathology and gene expression analysis should be added to the list of lung markers. When asked about the importance of his group's recommendations, Kleeberger stated that the suggestions would be good for NTP, NIEHS and the field in general. "From the perspective of lung biology and lung biomarkers, coming up with a series of markers that can be evaluated adds great value intramurally and extramurally," he said.

The next to report was the heart group, chaired by NIEHS's Bennett Van Houten. In addition to developing recommendations, the group proposed a decision tree to help investigators prioritize the tests they should do. Besides performing the standard histopathology on cardiac tissue, researchers should consider the following: serum troponin, rat α2-macroglobulin and serum ß-type natriuretic protein, perhaps in conjunction with echocardiography. Although all of the chairs agreed that some recommendations would be expensive to implement, Van Houten said cost wouldn't be a problem when incorporating the top three recommendations. "A lot of the biomarkers that we discussed are extremely easy to implement because the costs aren't exorbitant, but if you go to some of the more difficult ones such as gene expression profiling, then the costs are very high," he added.

The final group to report was lipid/carbohydrate metabolism, chaired by Sheila Collins from the CIIT Centers for Health Research. The recommendations included tests for cholesterol/triglycerides, insulin and reduced glutathione. Collins commented on the importance of the meeting for her discipline. She said, "It's been very good as an idea generator for expanding the effort to look at not only the classic toxicology markers, but to begin to look at such things as heart disease and lipid irregularities."

John Bucher of NIEHS said that all of the recommendations would be considered, but some would be implemented faster than others. "Tests such as the troponin assay are relatively simple," he said, "[but] others would require a little developmental work to make sure that they are technically feasible, sensitive enough and applicable in rodent studies."

Popp applauded the NIEHS staff for organizing the meeting and stated that this gathering may lead to a new era in toxicological testing. "NTP has made great contributions in the past in terms of study design and evaluation, in addition to the results that they've created," he said. "I predict that this [workshop] is going to be the beginning of setting a path forward, not only for NTP, but [for] toxicology programs across the nation."



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