While treating patients with cancer or other diseases resulting from genetic mutations, the biggest hurdle that doctors often face is that the drugs at their disposal do not discriminate between healthy cells and dangerous ones. The new research aims at searching a solution for this problem.
"When one of the two strands of our cellular DNA is broken, intricate cell machinery is mobilized to repair the damage," said Igor V. Alabugin, an Associate Professor of Chemistry and Biochemistry at the university.
"Only because this process is efficient can humans function in an environment full of ultraviolet irradiation, heavy metals and other factors that constantly damage our cells," he added.
However, a cell that sustains so much damage that both DNA strands are broken at the same time eventually will commit suicide, a process known as apoptosis.
"In our research, we're working on ways to induce apoptosis in cancer cells -- or any cells that have harmful genetic mutations -- by damaging both of their DNA strands," Alabugin said.
"We have found that a group of cancer-killing molecules known as lysine conjugates can identify a damaged spot, or 'cleavage,' in a single strand of DNA and then induce cleavage on the DNA strand opposite the damage site. This 'double cleavage' of the DNA is very difficult for the cell to repair and typically leads to apoptosis," he added.
He further said that the lysine conjugates' cancer-killing properties are manifested only when they are exposed to certain types of light, thus allowing researchers to activate them at exactly the right place and time, when their concentration is high inside of the cancer cells.
"So, doctors treating a patient with an oesophageal tumour might first inject the tumour with a drug containing lysine conjugates. Then they would insert a fiber-optic scope down the patient's throat to shine light on the affected area," he said.
Alabugin also said that the light exposure would activate the drug, leading to double-strand DNA damage in the cancerous cell and thereby triggering apoptosis. He said that for tumours located deeper within the body, a pulsed laser device could be used to penetrate muscle and other tissues, thereby activating the drugs using near-infrared beams of light.
Future work by the researchers will include demonstrating anti-cancer activity in an animal model which, if gives promising results, will pave the way for clinical trials with human patients.
A paper describing the results of the research, 'DNA Damage-Site Recognition by Lysine Conjugates', has been published in the journal Proceedings of the National Academy of Sciences.