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Scientists Say Flies May Replace White Mice in Cancer Labs

June 4, 1991

LONDON (AP) _ For the first time, scientists have inserted human genes into fruit flies with the hope that the flies will eventually replace rats and mice in cancer experiments.

The new twist in genetic manipulation is reported in this month’s issue of The EMBO Journal, the European journal of molecular biology.

The development could have vast implications for studying how environmental agents trigger cancer, how human enzymes fend off disease and how the body breaks down drugs, said Dr. Roland Wolf, a leading investigator at the Imperial Cancer Research Fund’s molecular pharmacology group at the University of Edinburgh.

What’s more, the one-milligram drosophila fruit fly is cheaper, has a very simple genetic system that lends itself to study, and is more ″socially acceptable than the rather unpopular mammal studies,″ said co-investigator Dr. Trevor Jowett, a geneticist from the University of Newcastle in northern England.

Experts said, however, that it would be several years before flies could conceivably replace rodents in the lab.

Dr. Spyridon Artavanis-Tsakonas, a Yale professor of cell biology and biology called the genetically altered fly experiment the first of its kind.

He said it ″may be jumping the gun″ to say flies will replace mammals in cancer testing, but ″it is not an unreasonable hope.″

″To what degree we can use flies to address humans remains to be seen, but my guess is that we will be astonished,″ Artavanis-Tsakonas added. He uses drosophila flies to investigate how cells in the nervous system communicate.

The British scientists teased rat and human genes for one enzyme system, cytochrome P450s, in between fly genes. The P450 system is the body’s first line of defense against chemicals, researchers said.

Strangely, it also alters seemingly harmless drugs into cancer-causing byproducts. Some drugs are harmless in their initial state, but are digested in the body to dangerous derivatives.

One such drug, cyclophosphamide, was used to test the new fly system. Scientists fed cyclophosphamide, a cancer drug, to flies. Sure enough, the drug sparked the P450 system in the altered flies, but did nothing in the normal flies.

The cyclophosphamide proved the system works. Now researchers want to transplant other human enzymes.

″There is nothing special about the P450, but we can take other enzymes and test them and learn about their relative importance in drug metabolism,″ said Jowett in a telephone interview.

This first altered fly experiment looks at the consequences of just one enzyme system. Potential cancer-causing agents and drugs affect a host of enzymes in much more complicated and still unknown ways.

Eventually, investigators say they will transplant a series of genes to study a cascade of events.

″This is the first step in generating a living model where the cancer- causing potential of chemicals can easily be identified and where the cascade of events leading to cancer can be understood,″ Wolf said.

The fly may help solve many mysteries about the way cancers grow and how anti-cancer drugs work. For instance, cancer patients frequently become resistant to cancer drugs, and doctors do not know why.

Scientists also want to know how certain chemicals damage DNA, the building blocks of genes. The simple genetic system of the fly allows scientists to insert one or two human enzymes, and then see if specific environmental agents or anti-cancer drugs damage DNA. Damaged DNA is thought to increase the likelihood of cancer.

″We can really start to understand the properties of carcinogens,″ said Wolf. ″All of these things will be able to show us the relative importance of specific genes in causing or blocking cancer.″

Currently, scientists study enzyme reactions in test tubes, or in test chemicals in rats or mice. However, rodents do not necessarily digest drugs or fight cancer-causing agents the same way humans do. Other scientists have inserted human genes into rodents.

Dr. James Mason, a National Institutes of Health geneticist at the National Institute of Environmental Health Sciences in Research Triangle Park, in North Carolina, said ″it will improve our abilities to understand the mechanisms used by humans to detoxify chemicals and really know what goes on in the body.″

But, he added in a telephone interview, it will be many years before the fly can substitute for the rat or mouse in cancer studies. Right now, these scientists have explored one enzyme system, but the human system is far more complex.

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