New Effects of Radon Exposure Uncovered

LAB RESEARCHERS UNCOVER NEW EFFECTS OF RADON EMISSIONS ON HUMAN CELLS

LOS ALAMOS, N.M., July 15, 1997 -- Los Alamos National Laboratory researchers have uncovered new evidence of how radioactive emissions from radon and its decay products induce cellular changes that could lead to cancer.

The results of an investigation reported in a recent issue of Cancer Research show that alpha particles like those emitted by indoor radon gas do not have to hit the nucleus of a cell to create changes that could damage the cell's DNA, which resides in the nucleus. In fact, the alpha particles don't even have to hit the cell; a microscopic bombardment of the surrounding medium can result in the production of chemicals that in turn induce cellular changes capable of causing DNA damage.

The researchers quantified the rate of cellular production of two highly reactive oxygen molecules -- superoxide, an electrically charged pairing of oxygen atoms, and hydrogen peroxide -- that could be involved in alpha particles' DNA-damaging effects.

"Our observations negate pre-existing assumptions that alpha particles like those emitted by radon and radon progeny exert their genetic changes exclusively through direct traversals of cell nuclei," said Los Alamos' project leader Bruce Lehnert. "Accordingly, current dosimetry models upon which environmental standards for radon exposure are derived now require serious reconsideration. Our work suggests that even interactions of alpha particles with the fluids that line the lungs may lead to alterations in the DNA of nearby cells."

Padmakumar Narayanan, Edwin Goodwin and Lehnert, all of Los Alamos' Cell and Molecular Biology Group, are co-investigators in the U.S. Department of Energy-funded alpha particle project.

This latest study continues an investigation by Los Alamos researchers into the possibility that alpha particles emitted by radon produce oxygen-based molecules that are chemically very reactive. These molecules could be the source of damage within a cell that sparks the onset of cancer.

Alpha particles consist of two protons and two neutrons bound together and can pack a microscopic wallop when they collide with molecules.

Researchers know of a number of different biological effects associated with exposure to alpha particles, but the exact mechanism by which alpha-particle exposure can lead to cancer has never been clear. There's been a long- standing assumption in scientific circles, however, that alpha particles strike DNA directly, damage it and consequently induce cancer.

The Los Alamos researchers studied normal human lung cells grown in a culture medium and exposed them to different amounts of alpha radiation. They then used flow cytometry to discern the amount of superoxide and hydrogen peroxide formed after the cells were exposed to alpha particles or to culture medium that was exposed to alpha particles.

Flow cytometry -- developed at Los Alamos and now a tool routinely used for molecular studies -- uses a laser beam to excite fluorescent markers that stain cellular components or molecules. When struck by the beam, the markers glow and the corresponding light is picked up by sensitive detectors. Measurements of the fluorescence allows researchers to determine quantitatively how much of the molecule of interest is present.

The Los Alamos study looked at two fluorescent molecules whose production is dependent on the presence of superoxide and hydrogen peroxide, respectively. The quantity of fluorescent molecules detected corresponded to the quantity of superoxide anions or hydrogen peroxide present.

The researchers learned that exposure to low doses of alpha emission increased the production of the reactive oxygen species superoxide and hydrogen peroxide within the cells. Although the response rate of superoxide production to the amount of the alpha dose was not linear, superoxide production increased significantly with alpha-particle exposure even at the lowest doses. Similar increases in cellular production of the reactive oxygen species were found with cells that were not directly irradiated but, instead, were treated with culture medium that had been exposed to a low dose of alpha particles

The research team determined where alpha particles hit the cells and showed that a direct hit on the nucleus was not necessary to generate production of hydrogen peroxide.

The team also irradiated the medium itself and found that it produced reactive oxygen forms. This suggests that even irradiation of material surrounding cells can create a potentially destructive environment.

"Extensions of our findings to the in vivo condition would suggest that inhaled radon and radon progeny may induce a condition of oxidative stress that is transmissible among lung cells and that may be involved in mediating DNA damage," the authors wrote.

Los Alamos National Laboratory is operated by the University of California for the U.S. Department of Energy. -30-