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New method of detecting damaged DNA wins `wows!’

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An extraordinarily sensitive tool for detecting damaged DNA is being hailed as a breakthrough in the understanding of how the body responds to genetic injury.

Within two weeks of the technology's description appearing in scientific literature, potential applications now being discussed include:- Providing a diagnostic tool to determine whether some workers in chemically hazardous industries are more at risk of cancer than others;

- Providing a step-by-step analysis to determine at what dosage a substance might tend to cause cancer or birth defects;

- Monitoring non-cancer cells that could be toughened to resist the lethal effects of radiation therapy.

"Studying other types of environmental toxins with this tool is going to be really popular," said Philip Hanawalt, a Stanford University biologist who has written the standard textbook on DNA dam-age. "This technique allows us to specifically measure just how low a level of toxic exposure we should be worried about. . . . It's an extremely exciting development, and that's just the tip of the iceberg."

In fact, researchers in fields as varied as toxicology and limnology (the study of freshwater bodies) have expressed keen interest in the tool.

"Scientists who understand the implications of this tool are just saying, `Wow,' " added David Schindler, a water ecologist at the University of Alberta who assesses the impact of low-level toxins on aquatic organisms.

DNA damage can be caused by a host of things, including a runner's overheated body, oxygen in air, sunlight and natural and synthetic chemicals. Constantly under siege, the body is a remarkably efficient repair shop, initiating more than 100,000 DNA repairs per cell per day. These same repair mechanisms become less efficient as people age, a deterioration that eventually can lead to cancer.

As reported in the May 15 issue of Science magazine, the University of Alberta scientists' ultra-sensitive technique is 10,000 to 100,000 times more powerful than current methods of measuring DNA damage.

This gives it the potential to allow scientists to study over time what they have just guessed at before: the progression in a body from reparable DNA injury to uncontrollable cancer.

"We have combined three existing biomedical techniques and used them in different ways to create a very powerful instrument to detect damaged DNA," said Chris Le, assistant professor in environmental-health studies at the University of Alberta's faculty of medicine and the key player in the technology's development.

The new technique works in three steps.

First, it highlights the damage with two antibodies - one created to label the damage and another fluorescent antibody designed to light up the damage-seeker.

Then, a small glass tube the size of a hair, in a process known as capillary electrophoresis, is used to separate all the molecules floating around the ravaged DNA with an electric charge.

Finally, a laser illuminates the fluorescent antibody attached to the damaged part so it can be detected. The brighter the light intensity, the greater the DNA damage.

In the Science article, Le, Michael Weinfeld and their university colleagues described using the technique, which relied on antibodies provided by microbiologist Tony Leadon at the University of North Carolina. The scientists were able to measure damage caused by previously undetectable levels of radiation.

With their novel instrument, the Alberta researchers found that levels of gamma radiation far below that used in cancer therapy damaged DNA in human lung cells. In what University of Alberta chemist Norman Dovichi described as an observation "that throws a curve at conventional wisdom," the group also found that slightly exposed cells built stronger defenses against higher doses.

This holds out the possibility, Leadon suggested, for "hardening" normal cells surrounding a tumor about to be dosed with radiation. Beyond its sensitivity, the new test can also locate DNA damage more cleanly than existing procedures. Today, the chemicals and enzymes now used to track down many DNA breakdowns often cause as much damage as they find.