Lithium may help radiation target cancer, spare heal...(r DNA but it can also attack the DNA of ...)

Date:5/4/2009

r DNA, but it can also attack the DNA of healthy cells. One of the most serious types of DNA damage is the chromosomal double-stranded break (DSB), in which both strands of the double helix are severed. Even a single unrepaired DSB can be lethal to a cell. Fortunately, the body has several different ways to repair DNA damage.

Xia, whose lab studies the mechanisms of DNA repair in normal cells and tumor cells, suspected that lithium might affect how DNA is repaired following radiation-induced damage.

Working with Eddy Yang, M.D., Ph.D., a resident in the Radiation Oncology department and an American Board of Radiology Holman Research Scholar, and postdoctoral research fellow Hong Wang, M.D., Ph.D., Xia and colleagues examined DNA repair in lithium-treated mouse hippocampal neurons exposed to radiation.

They found that lithium did not prevent the generation of DSBs but promoted a particular kind of DNA repair called nonhomologous end-joining (NHEJ) repair which is the predominant repair mechanism used by normal neurons. Xia and colleagues showed biochemical and genetic evidence that radiation-induced DSBs were repaired with greater efficiency in lithium-treated cells via the NHEJ pathway.

However, none of these effects were observed in malignant glioma (brain tumor) cells, presumably because cancer cells generally utilize a different DNA repair mechanism, Xia said.

The researchers confirmed these findings in mice treated with cranial radiation. The results suggest that lithium protects healthy hippocampal neurons by promoting NHEJ-mediated DNA repair but that lithium offers no protective effect in the brain tumor cells tested.

Since some tumors are resistant to radiation, Xia hopes that lithium treatment could provide a way to increase the radiation dose to levels that will kill the tumor cells while protecting healthy brain tissue. The team is launching an investigation of the safety and feasibility of lithium
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Contact: Melissa Marino melissa.marino@vanderbilt.edu 615-322-4747 Vanderbilt University Medical Center Source:Eurekalert

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