'One man's poison': genetic vulnerability.

"One man's poison': Genetic vulnerability

About a decade ago, in a Dupont plant in Deepwater, N.J., exposure to a chemical used in manufacturing caused 87 episodes of a potentially serious blood disorder in workers. But it wasn't a simple case of exposure equaling problems. Though many more workers were exposed, just 30 developed the disorder, and 30 of the episodes occurred in 8 workers. Now scientists are gathering tools to crack open the "black box' of why some people are predisposed to environmentally associated diseases. Some of those tools were described last week in Philadelphia at the annual meeting of the American Association for the Advancement of Science.

"Virtually all' of the common human-made compounds in the environment are metabolized by a complex group of enzymes called the cytochrome p-450 system, says Harry Gelboin of the National Cancer Institute in Bethesda, Md. These enzymes can convert a toxic chemical into a harmless metabolite--or a harmless chemical into a potent carcinogen. There is enormous individual variation in the amount and efficiency of the p-450s: The action of a given enzyme can vary three-fold among individuals, researchers say, affecting vulnerability to environmental toxins. But scientists have had trouble studying the system because of its complexity. Now, Gelboin says, his studies show that monoclonal antibodies are "a beautiful way of sorting out the multiplicity of forms and [of finding] which p-450 is responsible for which reaction.'

Vulnerability may also stem from an inability to repair DNA damage. Lawrence Grossman of Johns Hopkins University in Baltimore and his colleagues have designed an assay for DNA repair potential. In the laboratory, Grossman damages an enzyme-coding gene in Escherichia coli bacteria; then he introduces the gene into human cells in culture. Because humans don't normally produce the enzyme, any enzyme found reflects the cells' ability to repair the genetic damage. According to Grossman, the technique will provide evidence about the relationship between variations in DNA repair potential and susceptibility to environmental mutagens, agents that cause changes in DNA.

Says Daphne Kamely, of the Environmental Protection Agency, "If we come up with good enough science, if we can really say only this fraction of the population is at risk, then [the regulatory agencies] may say, "Maybe we shouldn't just ban this chemical entirely.'' Warnings could allow people to make choices about exposure, she says.

A number of ethical questions are tied like tin cans to the scientific advances. Some researchers note that the ability to profile individual vulnerability raises concerns--worries of workers about job discrimination, for example. But according to Gilbert Omenn of the University of Washington in Seattle, "There's an emerging consensus that you can deal with problems in the work place, if you do things stepwise. . . . And if a worker believes he or she is at higher risk, they might well be more motivated' to take self-protective measures.