ANAHEIM, CALIFORNIA--Many toxicologists can remember being dogged at some point by people opposed to chemical tests on animals, especially mammals. Now one researcher has moved a step closer to easing the disapproval that he and his colleagues often feel. At the annual meeting of the American Association for the Advancement of Science, which publishes ScienceNOW, aquatic toxicologist Richard Winn of the University of Georgia, Athens, described a promising new line of fish that may help replace rats for screening toxic chemicals.
To enhance their ability to detect the mutations chemicals might cause, in the mid-1980s toxicologists began using lab mice carrying bacterial genes that can be pulled out and screened for damage. This is much easier than, say, screening the entire mouse genome or waiting for tumors to develop. Hoping to find an alternative to rodents, Winn and his colleagues turned to medaka fish, which are already used for toxicology tests. They introduced into the animals two bacterial genes, called LacI and cII, used in lines of transgenic rodents to detect mutations caused by chemicals.
In early tests, they dumped the widely used mutagen N-ethyl-N-nitrosourea (ENU) into their fish tanks, and after waiting 1 to 16 hours, ground up the fish and retrieved the bacterial DNA for analysis. The researchers found that they could detect even slight genetic changes, charting a two- to threefold increase in mutations at low exposures to ENU. Winn also described a transgenic medaka with a third gene called LacZ that he says works well for detecting radiation-induced damage. Radiation tends to knock out or rearrange big chunks of DNA, and this gene is big enough--and its carrier, a circular piece of DNA called a plasmid, is sturdy enough--that there is sufficient DNA left for analysis after a radiation hit.
If the research pans out, it could not only save many mammals' lives, but also make toxicology testing cheaper and easier. Keeping a fish costs "pennies a year," compared to 20 cents a day per mouse, Winn says. "I was really thrilled" to hear about Winn's progress, says toxicologist Barbara Shane of Louisiana State University in Baton Rouge, who studies cancer in mice. She and others are eager to begin tests on transgenic medaka.