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Radiation's own version of chemotherapy.

Radiation's Own Version of Chemotherapy

Scientists have identified a previously unrecognized mechanism by which radiation indirectly kills certain tumor cells. "This is the first time you can explain radiation's mechanism of action by some means other than its direct effect on [a cell's] DNA," says Ralph R. Weichselbaum, the radiation oncologist who led the University of Chicago study. While noting that the findings are very preliminary, the researchers say they believe the toxic chemical they've isolated from irradiated human cancer cells may ultimately hold promise as a drug to boost radiotherapy's effectiveness.

Weichselbaum says his team happened onto the finding while conducting experiments on radiation survival of tumor cells. They found entire populations of cells dying from what should have been sublethal radiation exposures. After ignoring the problem for about six months -- initially suspecting it resulted from technician errors -- "I finally got the bright idea of decanting the [culture] medium" in which the cells grew, Weichselbaum says. When he added the cell-free fluid to new cultures of healthy cancer cells and observed that it immediately began killing these nonirradiated cells, he realized that the cells irradiated in the first tests must have manufactured some lethal poison.

In the December PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES (Vol.86, No.24), Weichselbaum and his co-workers describe their experiments kand identify the toxic substance as tumor necrosis factor (TNF)--an immune system protein normally made by the body to aid in healing or to fight infections and tumor growth. Other researchers are testing TNF as an anticancer therapy in humans, but to date it has shown little promise.

The Chicago team found that in some cell lines, adding TNF -- either before or up to four hours after irradiation -- to cells that hadn't initially produced it could increase the number of cells that ultimately succumbed.

The gene that triggers enhanced production of TNF "is the only mammalian gene found to have increased expression after exposure to ionizing radiation," the researchers assert. Weichselbaum told SCIENCE NEWS he hopes to determine exactly how irradiation activates this gene and several other candidate genes his group is investigating.

Some researchers, among them cancer biologist Keith Laderoute at SRI International in Menlo Park, Calif., argue that even before this study, scientists had identified at least one other mammalian gene -- coding for DNA repair -- as being activated by damage to DNA. However, he adds, the "intriguing" new report "does appear to show real, new effects -- that some tumors may be sensitized to radiation by TNF."

"This is certainly an interesting paper," comments radiobiologist Eric J. Hall at Columbia University in New York City, "though my reaction is guarded until the experiments are repeated in other systems" -- other cell types or animals. For example, though the Chicago team claims evidence of a potential synergy between radiation and TNF, Hall notes that the data presented in the research report suggest their effects may be merly additive, with the TNF killing off particularly radiation-resistant cells. "That isn't to say that the two together are not useful," he adds.

TNF is a cytokine, one of a group of powerful cell-secreted chemicals that include growth factors and interferon. But it is not the only cytokine shown to modify cancer cells' response to radiation, notes Robert M. Sutherland, a cancer biologist at SRI International. In the July 5, 1989 JOURNAL OF THE NATIONAL CANCER INSTITUTE, he and Tim Tak Kwok reported that the presence of epidermal growth factor -- a normally nonlethal cytokine -- enhanced the radiation sensitivity of human squamous carcinoma cells. Sutherland says the SRI and Chicago findings, taken together, appear to "open up an interesting new area worthy of more investigation" -- the role of natural cell-derived chemicals in modulating radiation sensitivity.
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Author:Raloff, J.
Publication:Science News
Date:Jan 13, 1990
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