The scientists first studied mice before radiation exposure. They found more than 130 genes that express differently in blood and mammary tissue samples of cancer-resistant mice compared to cancer-sensitive mice.

To determine if these differences also apply to people, the scientists mined human breast cancer “knowledge bases” that link the expression of patients’ tumor genes with their survival outcomes. They studied newly diagnosed women before they received radiation or chemical therapies. Women with gene expression levels like those of radiation-sensitive mice were less likely to survive after eight years. In contrast, women with expression levels like those of the resistant strain were more likely to survive the eight-year duration of the follow-up.

Next, gene expression analyses conducted a few hours after the end of low-dose exposure found changes in many genes in the mammary tissue of cancer-sensitive mice. Large numbers of genes that regulate their immune system were suppressed, while genes that regulate pubertal mammary gland development were turned on in error. In cancer-resistant mice, these genes showed only a small change in activity.

Analyses conducted one month after exposure yielded striking differences in the expression of a large set of genes that control cell proliferation. The cancer-sensitive mice had up-regulated many genes associated with cell division and cell renewal. The cancer-resistant mice had down-regulated these same genes below normal levels, which suggests they were able to activate tissue mechanisms that prevent cellular proliferation that can lead to cancer.

These differences again carried over to people. Breast cancer patients whose cell division and renewal genes were up-regulated like the cancer-sensitive mice didn’t survive as long as patients in which the same genes were suppressed.

The scientists are now refining these gene expression signatures by studying large groups of women with breast cancer. They’re also testing the mechanisms by which these signatures control radiation sensitivity using special breast cell culture models developed at Berkeley Lab.

“This research opens promising opportunities for developing blood tests that predict a woman’s risk for breast cancer, and which identify women who are susceptible to the cancer effects of low-dose radiation exposures,” says Wyrobek.

This research was supported by Berkeley Lab’s Laboratory Directed Research and Development fund and the Department of Energy’s Office of Science.

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Lawrence Berkeley National Laboratory addresses the world’s most urgent scientific challenges by advancing sustainable energy, protecting human health, creating new materials, and revealing the origin and fate of the universe. Founded in 1931, Berkeley Lab’s scientific expertise has been recognized with 13 Nobel prizes. The University of California manages Berkeley Lab for the U.S. Department of Energy’s Office of Science. For more, visit http://www.lbl.gov.

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Dan Krotz
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