This is an archive page. The links are no longer being updated.
Date: February 27, 1996 For Release: Immediate Contact: NIEHS: Tom Hawkins (919) 541-1402 or NTP: Sandy Lange (919) 541-0530
The new test should be able to differentiate more quickly between chemicals that do or don't cause cancer -- and do so cheaper and with many fewer test animals -- than can the standard two-year mouse and rat tests used today.
Announcing the first step in establishing an effective partnership today, National Institute of Environmental Health Sciences Director Kenneth Olden, Ph.D., said, "We still have a long way to go. We have to broaden representation and take a number of additional steps. But this is a first step that some thought impossible, so I'm optimistic."
The group's goal is to test and agree on lines of gene-modified or "transgenic" mice to determine the cancer-causing properties of chemicals. Current rodent tests are done with regular laboratory strains of rats and mice, using both genders and done over two years at a cost of $2 to $4 million or more. With time for designing the studies and analyzing the data, the bioassays can take five years or more.
The goals were explored at a meeting on February 9 at NIEHS headquarters in Research Triangle Park, situated between Chapel Hill, Raleigh, and Durham, N.C. The meeting brought senior scientists from federal regulatory agencies, NIEHS and the National Toxicology Program together with scientists and senior executives from industry with experience with transgenic mice, as well as scientists from Europe and Japan. NIEHS is one of the National Institutes of Health, the only one not headquartered in the Washington, D.C., area.
Corporate organizations represented were Boeringer-Ingelheim; Pharmacia & Upjohn, Inc.; Proctor & Gamble; Merck, Sharpe & Dohme; Glaxo Wellcome, Inc.; DuPont; Rohm & Hass; Taconic Farms, and CIBA Pharmaceutical.
U.S. government agencies represented were the Food and Drug Administration and the Environmental Protection Agency. Other participants included scientists from the Central Institute for Experimental Animals and the School of Medicine at Keio University in Japan, and the National Institute of Public Health and Environmental Protection in the Netherlands.
NIEHS scientists led by Raymond Tennant, Ph.D., Chief of the Laboratory of Environmental Carcinogenesis and Mutagenesis, have identified two transgenic mouse lines as potential models for carcinogenicity testing, which Dr. Tennant highlighted at the meeting. They are the p53 deficient line originally developed at Baylor University for research purposes, which can be used to detect mutagenic carcinogens, and the Tg.AC line, developed at Harvard University as a model that can be used to identify both mutagenic and nonmutagenic carcinogens.
Dr. Tennant and colleagues at NIEHS and NTP are testing a group of 15 chemicals, using these transgenic mouse models. These chemicals have already been tested in the traditional two- year bioassay, thus the results from the new transgenic bioassays can be compared to the previous bioassay data.
Satoshi Yamamoto, M.D., of Keio University, Tokyo, described the Japanese development of the Tg c-Ha-ras mouse line as a carcinogenic screen. Tatsuki Nomura, Ph.D., Director of the Central Institute for Experimental Animals, Kawasaki, Japan, presented work on applying transgenic mice in place of monkeys in polio vaccine safety screening.
Coen van Kreyl, Ph.D., of the National Institute of Public Health and Environment, Netherlands, presented work from his agency on mouse lines being bred and maintained for research and screening, including the XPA deficient transgenic mouse model.
Attendees discussed strategies by which transgenic models could be evaluated for carcinogenic screening and risk assessment. They also explored ways in which additional organizations and individuals interested in participating in the partnership might be identified.
George Lucier, Ph.D., Director of the Environmental Toxicology Program, NIEHS, said that the National Toxicology Program expects to be doing the traditional 2-year rat/mouse bioassays for some time to come. "But we would like to find ways of lessening our reliance on these."
Several pharmaceutical company representatives said finding an effective, more rapid carcinogenicity screen could speed development of life-saving drugs for patients and help maintain the profitability of drug development.
Representatives from two major federal regulatory agencies -- the Food and Drug Administration and the Environmental Protection Agency -- noted that although additional data needs to be developed on the new transgenic models, they indeed may be the wave of the future, at first in combination with traditional assays.
Dr. Olden, who serves as Director of both NIEHS and the National Toxicology Program, commented: "I would like to advance these models as fast as possible. The 8 to 10 chemicals a year that we can screen using the current bioassays are simply not enough compared to the number of chemicals in the marketplace, and the cost of doing even these 8 to 10 is high. If we could reduce the cost by one-third, we could do more things with that money. So I think this is urgent to us, and to the health needs of the American people."