DIT researchers are trying to prevent radiation treatment causing damage to surrounding tissue. It could lead to more refined cancer targeting, writes Dr Claire O'Connell
Sometimes scientific research is like a good detective novel, full of secret messages, tantalising clues and unwitting victims. For example, researchers at Dublin Institute of Technology (DIT) are currently hunting down leads to find out how irradiated cells transmit mysterious signals that can lead to changes in "bystander" cells which have not been directly exposed to radiation. They hope their sleuthing could ultimately lead to more refined radiotherapy in cancer treatment.
The energy of ionising radiation directly damages cells by breaking chemical bonds within the cell's molecules, including DNA. In addition, water in the cell becomes ionised, resulting in reactive molecules that act like buzz-saws in the cells, causing indirect damage. It is also believed that irradiated cells send out one or more chemical signals that can induce damage in other, un-irradiated cells, which is known as the "bystander effect".
To catch these signals in the act, the DIT researchers irradiated human cells growing in a liquid nutrient solution called "medium" in the lab, explains Dr Fiona Lyng, who manages the Radiation and Environmental Science Centre at DIT's Focas Institute. After an hour they removed the medium from the irradiated cells and put it onto normal cells.
"The way we think of it is that the irradiated cells produce stress-induced signals into the medium and when you remove that to the other cells they are in the environment of something that has been irradiated," explains Dr Lyng. Factors carried over in the switched medium can induce a range of responses, including enhanced cell growth, DNA damage or cell death, she says.
The DIT group, which receives funding from Cancer Research Ireland and St Luke's Cancer Research Institute, also looked at the potential for bystander effects in living tissues.
They found irradiated bladder tissue from mice could induce bystander effects on unirradiated cells in the lab. "The tissue was still producing factors long after it had been irradiated and taken totally out of the body," she says. She adds that DIT post-doc Dr Orla Howe has started a study with St Vincent's University Hospital using cells from blood samples of patients before and after radiotherapy for colorectal cancer. "It's very early days," says Dr Lyng. "We want to see if some factor is released into the blood."
The signal or process that tells the unirradiated bystander cells to change is still something of a mystery, according to Dr Lyng, and the DIT group has carried out numerous experiments in lab-grown cells to look for clues.
For example, antioxidants that quell damaging reactive molecules can turn off bystander effects in receiving cells, says Dr Lyng. And calcium appears to be a prime suspect in kicking off biochemical pathways that tell the normal cell how to respond to the irradiated medium.
The researchers have identified biochemical pathways that the irradiated medium activates in normal cells, and have found blocking individual pathways can either rescue the cells or make them more likely to die. Being able to turn bystander effects up or down could ultimately have important medical uses, according to Dr Lyng. "In tumours maybe you would want to increase bystander signalling so you would kill more cells," she says. "And in the normal tissue surrounding the tumour you could want to turn off the bystander effects so that they don't get the effects of radiation."
She believes that the observation that bystander effects can result in cell death at low doses of radiation should prompt us to revise our opinions of safe exposure levels.