A Galway team has developed a way to detect if a person has been exposed to toxic cadmium, a substance that can sometimes pollute water courses, writes Claire O'Connell
The human body can find a good use for most chemical elements, but not for cadmium. The metal is toxic at high doses and has been linked to cancer.
Now researchers at NUI Galway have developed an ingenious "biosensor" system where specially treated cells light up if genes are switched on after cadmium exposure. They hope their approach will improve our ability to look at the biological effects of the metal in contaminated environments.
Cadmium can be an environmental pollutant around mining areas, and is also present in tobacco cigarettes and nickel-cadmium batteries. It can accumulate in bodily tissues over time and has been linked with prostate and lung cancer.
Ongoing research at NUI Galway is showing that when human prostate cells in the lab are exposed to low doses of cadmium, genes are switched on or off, says Dr Michael Carty, a lecturer at the department of biochemistry. "Certainly at high doses cadmium is toxic, but at doses that aren't overtly toxic there are still effects," he says. To help monitor the cellular effects of cadmium at low levels, the group has developed a biosensor that can indicate whether cadmium exposure activates genes within cells. "The idea of the biosensor is to make a cell line that when treated with relatively low levels of cadmium will generate a readout, which is the effect on [ the activation] of particular genes," says Carty.
To make the biosensor, the researchers took a standard cell line derived from human cervical cancer cells, explains Dr Antoinette McGee, who developed the system as part of her PhD project. Next they inserted a specially constructed piece of DNA into the cells. This stretch of genetic material contains a sequence called a "metal response element", or MRE, which is switched on in the presence of metals including cadmium.
To measure whether the MRE is turned on, the inserted stretch of DNA also includes a linked reporter gene called firefly luciferase, which makes a substance that gives fireflies their characteristic light.
Once the biosensor cells have been exposed to cadmium, the researchers do a simple test to see if the luciferase is producing light in the cells, explains McGee. If the cells light up, it means the luciferase gene has been turned on. This signals that the nearby MRE has also been turned on and means that cadmium is having an effect on gene activation.
"It's a very simple assay to just detect light," she says. "You check the slide and say whether we got a response."
The biosensor system can pick up gene activation at cadmium exposures as low as 0.5 micromolar, a level that would not be considered toxic to the cells, according to McGee. Their cell-based approach is around 20 times more sensitive than conventional toxicity tests for looking at biological effects, she adds.
The researchers hope the biosensor system could in future be used to help monitor cadmium levels around potentially contaminated environments such as mine tailings or landfills, states Carty. "I think the applications would be in monitoring the water or other contaminated areas to get a better idea of what the biological effects of those levels of contamination are," he says.
The project received funding from the Higher Education Authority.