Radiation's Collateral Damage

Ionizing radiation can do scary things to a cell's nucleus, shuffling or deleting large chunks of DNA in ways that can turn cells cancerous. Radiation that misses the nucleus and hits only the cell's cytoplasm, however, has seemed harmless. But a study in tomorrow's Proceedings of the National Academy of Sciences suggests ionizing radiation can stir up chemical changes in cytoplasm that lead to DNA damage.

For most people, the risk of absorbing excess ionizing radiation comes mainly through breathing radon, a gas released by uranium and thorium in soils. It may cause up to 21,600 cases of lung cancer each year in the United States. For decades, experts thought the alpha particles released by radon didn't affect the cell's cytoplasm. Then, in the early 1990s, scientists noticed that when they blasted cells with alpha particles, mutations cropped up even in cells that had not been directly hit. Called the "bystander effect," the findings led to speculation that the radiation was creating some agent in the cytoplasm--an unidentified chemical--that then damaged nuclear DNA.

Now scientists have homed in on what seems to be happening. Columbia University's Tom Hei and collaborators dyed hybrid human-hamster cells so they could see the nuclei, then sent a microbeam of alpha particles only to the cell's cytoplasm. Tests showed that the DNA of the cells was damaged, but that the mutations were smaller than would be expected with a nuclear hit--resembling spontaneous mutations. Hei's group suspected that the radiation creates reactive oxygen species that somehow damage DNA. And indeed, adding a solvent to the cells that scarfed up oxygen prevented the mutations.

This kind of injury might be more dangerous than direct nuclear damage because a higher fraction of cells survive, so more cells could eventually turn cancerous, Hei says. But the results don't necessarily mean that radon is any more dangerous than previously estimated. That's because the risk level is set using studies of cancer rates among people exposed to radon--not cellular studies.

"It's an interesting paper. Thought-provoking," muses Helen Evans, a radiation biologist at Case Western Reserve University in Cleveland, Ohio. But she's baffled by how free radicals--which have very short lifetimes and travel short distances--could reach the nucleus of even adjacent cells in time to inflict DNA damage.

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