Low doses of radioactivity led to healthier pups

By Tina Hesman Saey

Web edition: November 6, 2012

X-rays may not heal broken bones, but low doses of ionizing radiation may spark other health benefits, a new study of mice suggests.

Radiation in high doses has well-known harmful effects. Scientists had thought low doses would do less extensive damage but could add up to big problems later. But radiation acts differently at low doses, producing health benefits for mice with an unusual genetic makeup, Randy Jirtle of the University of Wisconsin–Madison and colleagues report online November 1 in the FASEB Journal. Antioxidant vitamins, such as vitamins C and E, erased those health gains.

“What goes on at high doses is not very predictive of what happens at low doses,” says Edward Calabrese, a toxicologist at the University of Massachusetts-Amherst. Chemicals that are poisons at high doses may be growth or health promoters at low concentrations. “It’s a major observation that is still to be appreciated,” he says.

Jirtle’s group studies mice known as viable yellow agouti mice. Scientists use them to gauge how diet, chemicals and other environmental conditions affect gene activity in animals, probably including humans. Agouti mice have a genetic quirk that causes the agouti gene to be turned on in all their body tissues. This results in yellow coats, obesity, diabetes and more cancer than normal. But attaching chemical tags to the DNA, a process called DNA methylation, around the agouti gene shuts the gene’s activity down, leading to lean, brown, healthy mice. Chemicals, stress or other factors that interfere with methylation shift the coat color and health status of the mice.

The scientists irradiated pregnant mice so that developing fetuses received doses between 0.4 centigrays and 7.6 centigrays. (A human dental X-ray delivers about 0.4 to 0.8 centigrays.) Some mice were put in the scanner but not irradiated. Mother mice that got radiation doses between 0.7 and 3 centigrays had more pups with browner coats than did sham-irradiated mice. Browner coat colors among mice exposed to low-dose radiation were associated with higher levels of DNA methylation on the agouti gene, indicating that radiation does something to alter the chemical tagging.

Giving mother mice antioxidants blocked the tagging. That finding could mean that radiation is creating oxidants, chemicals that are hungry to interact with other molecules. Too many hungry molecules in a cell can tear apart proteins, DNA and other components, but small numbers of oxidants serve as chemical messengers for cells. In this case, low-level radiation may have signaled cells to shut down agouti activity, thus making the mice healthier. Vitamins and other antioxidants that intercept that message would promote the unhealthy state.

Jirtle wasn’t exactly excited about the result at first. “Nobody wants to think that low dose radiation could be advantageous and the stuff you put in your vitamin pill would be bad,” he says.

Although the mice in Jirtle’s experiments have a specific genetic quirk that may make low levels of radiation helpful to them, people may also get some benefits from such exposure, Calabrese says. Before antibiotics became widespread, some doctors treated ear and sinus infections and gangrene with low dose X-rays. Low doses of radiation are also sometimes used to treat arthritis in people who can’t take anti-inflammatory drugs. Radiation may help modulate the immune system by altering epigenetic tags on DNA in immune cells, he says.