Low-dose radiation better at killing cancer cells

A new study shows that lower doses of radiation elude a damage detection 'radar in DNA and actually kill more cancer cells than high-dose radiation, according to an Oct 4, 2004, news release from Johns Hopkins Medicine, Baltimore. Based on these findings, scientists believe they can design therapy to dismantle this radar sensor, allowing more radiation to evade detection and destroy greater numbers of cancer cells.

Researchers at the Johns Hopkins Kimmel Cancer Center tested the tow-dose radiation strategy on cultured prostate and colon cancer celt tines that 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, and high doses are 1,000 times stronger. Approximately 35% of colon cancer cells survived low-dose radiation, compared to 60% receiving high-dose radiation. In prostate cancer cell lines, half of the cells survived tow-dose radiation, and 65% survived in higher doses.

The extra lethality of the low-dose regimen was found to result from suppression of a protein called ataxia telangiectasia mutated (ATM), which works like a radar to detect DNA damage and begin repair. In the low-dose group, ATM activation was reduced by 40% to 50%. The researchers proved ATM inactivation was the culprit because low-dose irradiated cells fared better after ATM was reactivated with chloroqine, a medication best known as a treatment for malaria.

Researchers speculate that cells hit with small amounts of radiation fail to switch on the ATM radar, preventing an error-prone repair process. Higher doses of radiation cause extreme DNA damage and widespread celt death, so the ATM damage sensor is activated to preserve as many cells as possible, protecting the cancer cells under target for destruction by the radiation.

Although the low-dose regimen works in cultured cells, it has not proved successful in humans. This has led to efforts by Johns Hopkins scientists to study ways to use viruses to deliver ATM-blocking drugs to the cells.

Low-Dose Radiation Evades Cancer Cells' Protective "Radar" (news release, Baltimore: Johns Hopkins Medicine, Oct 4, 2004) http://www.hopkinsmedicine.org/Press_releases/2004/10_05c_04.html (accessed 18 Oct 2004).

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