Low Dose Radiation More Effective at Killing Cancer Cells than HigherDoses

["Stabin, Michael" <michael.g.stabin@vanderbilt.edu>]

http://interactive.snm.org/index.cfm?PageID=3115&EID=1191401



Study Finds Low Dose Radiation More Effective at Killing Cancer Cells

than Higher Doses

Posted October 5, 2004 

Source: Johns Hopkins Medical Institutions



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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. With these findings, scientists believe they can design

therapy to dismantle this "radar" sensor allowing more radiation to

evade detection and destroy even greater numbers of cancer cells. 



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 (ataxia telangiectasia

mutated) which works like a radar to detect DNA damage and begin repair.





Theodore DeWeese, MD, 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, chairman of the

Department of Radiation Oncology and Molecular Radiation Sciences at

Johns Hopkins, presented his evidence at the annual meeting of the

American Society for Therapeutic Radiology and Oncology (ASTRO) on

October 5 in Atlanta. 



"DNA repair is not foolproof-it can lead to mistakes or mutations that

are passed down to other generations of cells," DeWeese explained. "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 targeted 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. 



In the current study, colon and prostate cancer cell lines were treated

with either high levels of radiation or small amounts spread over many

days. Low-level radiation is defined as 10 times more stronger than

normal background exposure, while high doses are 1,000 times stronger.

Approximately 35 percent of colon cancer cells survived low-dose

radiation as compared to 60 percent receiving high-dose. In prostate

cancer cell lines, half of the cells survived low-dose radiation, while

65 percent survived higher doses. 



In the low-dose group, ATM activation was reduced by 40 to 50 percent.

The researchers proved ATM inactivation was the culprit since low-dose

irradiated cells fared better after ATM was reactivated with chloroqine,

best known as 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," says DeWeese. 



This research was funded by the National Cancer Institute. 



Research participants from Johns Hopkins include Spencer Collis, Julie

Schwaninger, Alfred Ntambi, Thomas Keller, Larry Dillehay, and William

Nelson. 



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Michael G. Stabin, PhD, CHP

Assistant Professor of Radiology and Radiological Sciences 

Department of Radiology and Radiological Sciences 

Vanderbilt University 

1161 21st Avenue South

Nashville, TN 37232-2675 

Phone (615) 343-0068

Fax   (615) 322-3764

Pager (615) 835-5153

e-mail     michael.g.stabin@vanderbilt.edu 

internet   www.doseinfo-radar.com



 

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