When carcinogens enter the body and are activated, they can react with the DNA to form DNA adducts, chemical compounds in which the carcinogen is attached to the DNA. If the body’s natural defense systems do not properly repair the damage caused by these adducts, the result can be the birth of a renegade cell. Uncontrolled proliferation of such a cell results in cancer.

A reliable way to assess cancer risk is to keep track of DNA adducts formed in human cells. Gerald Small, an Ames Laboratory senior chemist and an Iowa State University distinguished professor, and Ryszard Jankowiak, an Ames Laboratory senior scientist, are developing a new means for detection of certain DNA adducts that can be found in urine. The newly developed biosensor chip technique is simpler and potentially more practical than previously developed methods.

"This scientific advance holds the promise of making it easier and less expensive to identify cancer-causing chemicals in the body, giving physicians a warning sign before the cancer grows and spreads," said Secretary of Energy Spencer Abraham.

Jankowiak leads the biosensor chip research project, which also includes Marc Porter, an ISU chemistry professor and director of ISU’s Microanalytical Research Center. Jeremy Kenseth, who recently received his Ph.D. under Porter’s supervision, and Scott Duhachek, a former postdoctoral fellow who worked with Small and Jankowiak, also made significant contributions to the project.

The biosensor technology is based on a unique gold chip that was constructed by Kenseth. The chip can be used to detect fluorescent DNA adducts – adducts that emit light when excited by a laser. Bound to the chip’s surface are special antibodies, proteins that serve as the body’s natural defense system against infectious agents. Scientists can develop antibodies in the laboratory to be so selective that they will preferentially bind a specific DNA adduct.

With the new biosensor chip technology, scientists could test for the presence of a certain adduct in a sample of urine by simply dipping a chip containing the corresponding antibody into processed urine. The adducts of interest would bind to the antibody and fluoresce when scanned with a laser beam at low temperature – 4 Kelvin (minus 452 F). The data gathered from the laser scanning would then be used to produce a detailed fingerprint for adduct identification, providing vital information for cancer risk-assessment.

"The biosensor chip technology has the potential to play a significant role in the advancement of cancer research," said Ames Laboratory Director Tom Barton. "It demonstrates, once again, the diversity of Ames Laboratory’s scientific efforts and the commitment of our scientists to perform cutting-edge research that may improve the lives of people throughout the world."

Jankowiak explained that initially they were unable to detect fluorescence at room temperature. However, he noted that the addition of a thin layer of glycerol to the surface of the chip led to a dramatic increase in fluorescence intensity at room temperature. "Cooling the chip further increased the intensity by a factor of 10," he said.

The research team is also investigating other enhancements to the biosensor chip technology, including making chips with several addresses for different antibodies that bind different adducts and using surfaces other than gold. "The more adducts that can be identified, the more complete the picture of DNA damage resulting from exposure to mixtures of carcinogens," said Small.

"We are currently looking at adducts implicated in breast and prostate cancer," said Jankowiak. "One day this technology, if commercialized, could lead to significant advances in pre-cancer diagnosis."

This work has been funded by the Energy Department’s Office of Biological and Environmental Research as part of its advanced instrumentation program that applies the technological expertise in the department’s national laboratories to problems of the nation’s health. Additional support for this work has been supplied by the National Cancer Institute.

Ames Laboratory is operated for the Department of Energy by Iowa State University. The Lab conducts research into various areas of national concern, including energy resources, high-speed computer design, environmental cleanup and restoration, and the synthesis and study of new materials.

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