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NTP: High Throughput Screening

By Blondell Peterson
January 2006

The National Toxicology Program continually seeks new ways to test for the toxicity of more compounds that make up potentially live-saving drugs each year. High Throughput Screening promises to alleviate the bottleneck effect in the discovery process because it allows a researcher to effectively conduct hundreds of experiments at once through a combination of modern robotics and other specialized laboratory hardware.

The NTP sponsored a HTS Assays workshop Dec. 14-15 in Crystal City, Virginia to provide information about HTS techniques and discuss using the technology for NTP toxicology screening. The workshop was held in conjunction with the formation of a NTP HTS Faculty at the National Institute of Environmental Health Sciences.

The main purpose of the Faculty is to:

  • develop and implement a strategy for the use of HTS assays by the NTP,
  • serve as the focal point for the design and evaluation of proposed HTS studies carried out by the NTP, and
  • serve as an interface between NTP and the NIH Molecular Libraries Initiative.

While attending the workshop, Raymond Tice, deputy director of the NTP Interagency Center for the Evaluation of Alternative Toxicological Methods, unveiled another dimension to the Faculty which he said would expedite the development of HTS assays with the NTP. Tice saidcientists outside of NIEHS will be invited to join the HTS Faculty in order to take advantage of their experience with the technology and exchange ideas. For example, pharmaceutical scientists use HTS assays to identify a compound for future development, and they typically focus on strong interactions and not toxicity. Therefore, they test at lower doses using relatively few assays. When testing for toxicity, NTP scientists must test at higher doses and use many more assays in order to not miss potential toxic effects. Tice said that pharmaceutical scientists have a wealth of experience using HTS techniques, and this knowledge can benefit NIEHS researchers in the NTP as the HTS Faculty begins to develop and apply this technology through assays.

"We are trying to identify assays that might help us predict toxicity like cancer or reproductive effects," Tice said. "So we hope the HTS is going to help us identify chemicals we think should have priority for future comprehensive testing."

According to Tice, the NTP began this task by sending 1,408 chemicals to the MLI at the NIH. The NTP has toxicological data for these chemicals. The chemicals will be run through several assays that may be of interest to NIEHS based on the pathway that is pertinent to the kinds of diseases scientists want to prevent. The data that is collected will be stored in a mutually-accessible database.

The NTP joined forces with the NIH MLI in August of 2005. This collaboration assisted the MLI project leaders with development of their screening program, and it provided the NTP with access to established testing laboratories.

The HTS Faculty will meet monthly. Individuals interested in joining the HTS Faculty should contact Tice at tice@niehs.nih.gov. According to Tice, the goal is for the Faculty to include representatives from each major program within the NIEHS. The first meeting will be held in late January 2006. Periodically, the Faculty will hold joint meetings with scientists at EPA who also are involved in the development of HTS assays for toxicological testing. Such meetings will help scientists in both organizations work toward a common goal.



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