Researchers at the Johns Hopkins Kimmel Cancer Center 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* which works like a radar to detect DNA damage and begin repair.
Theodore DeWeese, M.D., who led the study, speculates that cells hit with small amounts of radiation fail to switch on the ATM radar, which prevents an error-prone repair process. DeWeese, who will present his evidence at the annual meeting of the American Society for Therapeutic Radiology and Oncology on October 5 in Atlanta, explains.
"DNA repair is not foolproof - it can lead to mistakes or mutations that are passed down to other generations of cells," explains DeWeese, chairman of the Department of Radiation Oncology and Molecular Radiation Sciences at Johns Hopkins. "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, so the ATM damage sensor is activated to preserve as many cells as possible, protecting, ironically, the cancer cells under target for destruction by the radiation.
While the low-dose regimen works in cultured cells, it has not proved successful in humans. This has lead to effort by Hopkins scientists to study ways to use viruses that can deliver ATM-blocking drugs to the cells. Tests in animals are expected to begin soon.