DNA research highlights prostate cancer mechanisms

The number and intensity of the dash-shaped marks in the lower right corner of these DNA profile patterns indicates that normal cells (top) are more active in removing damaged DNA than two different lines of prostate cancer cells (center and bottom).

Certain prostate cancer cell lines are unable to repair DNA damage caused by "free radicals," according to scientists at the National Institute of Standards and Technology (NIST) and National Institutes of Health (NIH). This type of damage has been implicated before in the development of prostate cancer, but the new research, described in the March 25 online edition of Carcinogenesis, provides the first solid evidence that the normal repair process is altered in prostate cancer cells, possibly leading to a cascade of events that culminate in further DNA damage and cellular dysfunction.

Free radicals---highly reactive molecules generated by both normal metabolism and external sources such as chemicals and ionizing radiation---produce more than 30 different types of lesions in the nitrogen-containing compounds or "bases" of DNA. The damage is generally repaired in normal cells of young, healthy people. The NIH/NIST study examined four types of lesions in DNA from both cell nuclei and mitochondria, the energy factories of cells. The scientists found that prostate cancer cells unexposed to ionizing radiation had high levels of free radical damage and defective repair mechanisms. They also found that, after exposure to ionizing radiation and a repair period, prostate cancer cells exhibited elevated levels of free radical damage and reduced removal of lesions.

Prostate cancer is the most common form of cancer among American men. The new findings may help to explain the molecular mechanisms underlying the disease and support the idea that free radical damage and repair are "critical factors" in its development. The findings also have implications for possible therapies, supporting the theory, for instance, that selenium---a trace element that is a constituent of antioxidant enzymes---may be useful in preventing prostate cancer.

NIST's primary role in the study was to measure the types and levels of DNA damage. NIST pioneered the development of methods for detecting and measuring free radical damage at levels less than one base per million bases. The research was led by the National Institute on Aging.