Lower doses of radiation do not activate a protein that detects DNA damage and thus may actually kill more cancer cells than high-dose radiation, according to a presentation at the annual meeting of the American Society for Therapeutic Radiology and Oncology. The researchers believe they can build on the current findings to design therapy that is even more effective in killing cancer cells.

The American investigators tested the low-dose radiation strategy on cultured prostate and colon cancer cell lines and found that it killed up to twice as many cells as high-dose radiation. The extra lethality of the low-dose regimen was found to result from suppression of a protein, called ATM (ataxia telangiectasia mutated), that detects DNA damage and initiates repair.

Theodore DeWeese, MD, who led the study, speculates that cells hit with small amounts of radiation fail to switch on the molecular detection system. DeWeese explained "DNA repair is not foolproof − it can lead to mistakes or mutations that are passed down to other generations of cells. A dead cell is better than a mutant cell, so if the damage is mild, cells die instead of risking repair."

Higher doses of radiation cause extreme DNA damage and widespread cell death, activating the ATM damage system to preserve as many cells as possible, including malignant ones.

Although the low-dose regimen works in cultured cells, it has not proved successful in humans. This has led to an effort by scientists to study ways to use viruses that can deliver ATM-blocking drugs to the cells. Tests in animals are expected to begin soon.

In the current study, colon and prostate cancer cells lines were treated with either high levels of radiation or small amounts spread over many days. Low-level radiation is approximately 10 times more powerful than normal exposure, while high doses are 1,000 times stronger. Approximately 35 percent of colon cancer cells survived low-dose radiation compared with 60 percent receiving high-dose. In prostate cancer cell lines, half of the cells survived low-dose radiation, while 65 percent remained in higher doses.

In the low-dose group, ATM activation was reduced by 40 to 50 percent. The researchers proved ATM inactivation was the cause of cell death because low-dose irradiated cells fared better after ATM was reactivated with chloroquine, a treatment for malaria.

"Tricking cancer cells into ignoring the damage signals that appear on its radar could succeed in making radiation more effective in wiping out the disease," concluded DeWeese.