'Ames II' Can Detect the Precise Mutation Caused by a Chemical

by Robert Sanders

The Berkeley laboratory that nearly 20 years ago developed the first quick screening test for potential carcinogens has come up with an improved version--called Ames II--that is more sensitive and more specific than the original.

The original Ames test, reported in 1975 by Berkeley biochemist Bruce N. Ames and his colleagues here, was intended as a quick, reliable screen for chemicals that cause mutations in the genetic material DNA and thus could potentially cause cancer in humans. It was based on simple assay for mutations in the DNA of a common laboratory strain of bacteria.

The test revolutionized the field of genetic toxicology and was quickly adopted as a standard by everyone from government laboratories to industry to identify potentially harmful chemicals. Today a negative Ames test is required by many governments around the world, including the US Environmental Protection Agency and the Food and Drug Administration, before a chemical or drug can be marketed.

It also presaged a slew of similar tests using other types of cells.

The Ames test has remained the benchmark, however, in large part because it is simpler than most other available tests.

The Ames II assay uses the same bacteria--a strain of salmonella bacteria that infects mice--but is able to detect the precise mutation caused by a chemical.

"The new test tells you not only whether it's a mutagen, but what the change is," says Ames, a professor of molecular and cell biology. "What we get is a footprint, which offers a clue to what the mutagen was."

Gee, Ames, and retired research scientist Dorothy Maron reported their success in the Nov. 22 issue of the Proceedings of the National Academy of Sciences.

Though the original Ames test was not patented, the University of California has patented the Ames II assay and licensed it to Xenometrix, which recently began marketing it.

Ames notes that the test only detects those carcinogens that cause cancer by creating a genetic mutation directly. There may be another class of chemical that causes cancer by killing cells and as a result stimulating the remaining cells to divide. This enhanced cell division increases the possibility of a chance mutation occurring during the process of DNA duplication, and the subsequent development of cancer.

This may explain why many chemicals that test negative on Ames I nevertheless cause cancer in rodents at high doses. Many chemicals that are relatively harmless at low levels may induce cancer at very high doses through this mechanism, he says.

The work was sponsored by the National Cancer Institute and the National Institute of Environmental Health Sciences.

Berkeley Research in the Marketplace

The commercial introduction of the Ames II test to screen for potential carcinogens is one of several Berkeley inventions that have recently made it to the marketplace or are heading in that direction.

Last month, a private Boston-based biotechnology company announced the issuance of a patent for the use of an "anti-freeze" protein developed by Berkeley's Boris Rubinsky, a professor of biomedical and mechanical engineering.

The proteins are derived from fish that have evolved to survive in sub-freezing Antarctic water. It's envisioned the proteins could be used to preserve human and animal cells under frozen conditions as well as for such novel uses as creating new kinds of skin-care products to prevent frostbite. The patent is owned by UC, but products will be marketed by A/F Protein, Inc.

In addition, Microsoft Corp. is now selling ergonomically designed keyboards developed by researchers at the UC Ergonomics Lab at the Richmond Field Station. Developed to ease the stress of typing, the new design features a wide, split keyboard.

And finally, a technique for miniaturizing DNA diagnostic devices first demonstrated in the laboratory of chemistry professor Richard Mathies is heading closer to commercial development.

A consortium of businesses and universities, including Berkeley, is working toward developing a hand-held unit capable of analyzing the structure of a patient's DNA for diagnostic information.