Lithium, a drug widely used to treat bipolar mood disorder, may also help radiation target cancer and spare healthy tissue, according to a study.
Vanderbilt-Ingram Cancer Center researchers say that their work has uncovered a mechanism that helps explain how lithium protects the brain from damage that occurs during radiation treatments.
Lead researcher Dr. Fen Xia has shown that lithium promotes DNA repair in healthy cells but not in brain tumour cells, which suggests that lithium treatment could offer a way to protect healthy brain tissue from damage that may occur during cranial radiation treatments.
A previous study led by Dr. Dennis Hallahan, chair of Radiation Oncology and the Ingram Professor of Cancer Research, had found lithium treatment to protect cultured hippocampal neurons from radiation-induced cell death, and to improve cognitive performance in irradiated mice.
However, the researchers were still unclear as to how lithium protects against radiation-induced damage.
Describing their study in a research paper, the researchers highlight the fact that 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. They say that even a single unrepaired DSB can be lethal to a cell.
Working in collaboration with Dr. Eddy Yang, a resident in the Radiation Oncology department and an American Board of Radiology Holman Research Scholar, and postdoctoral research fellow Dr. Hong Wang, Xia examined DNA repair in lithium-treated mouse hippocampal neurons exposed to radiation.
The researchers observed 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 said that the study produced biochemical and genetic evidence that radiation-induced DSBs were repaired with greater efficiency in lithium-treated cells via the NHEJ pathway.
The researcher, however, admitted that none of the effects were observed in brain tumour cells, presumably because cancer cells generally utilize a different DNA repair mechanism.
The findings were confirmed in mice treated with cranial radiation, and the results suggested that lithium protects healthy hippocampal neurons by promoting NHEJ-mediated DNA repair - but that lithium offers no protective effect in the brain tumour cells tested.
Given that some tumours do not get affected by radiation, the researchers believe that lithium treatment may provide a way to increase the radiation dose to levels that will kill the tumour cells while protecting healthy brain tissue.
Xia and colleagues are planning a study of the safety and feasibility of lithium treatment in patients with low-grade glioma or brain metastases from small cell lung cancer.
"Right now, the problem is that we cannot kill the tumour completely because normal tissue toxicity limits the dose. So if we can protect normal tissue, we can hopefully give a higher dose to the tumour," Xia said
The study has been reported in the Journal of Clinical Investigation.