It is known that radiation can cause cancer by damaging DNA. According to a recently published study, radiation might also induce other molecular changes in surrounding tissue. Such molecular changes were associated with accelerated tumor growth and with the development of a particularly aggressive type of breast cancer in a mouse model of breast cancer (Cancer Cell 19, 640–651; 2011).

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Mary Helen Barcellos-Hoff of the New York University School of Medicine and colleagues exposed a group of 10- to 12-week-old mice to whole-body radiation at doses of 10–100 cGy. Three days later, they transplanted oncogenic tissue into the mammary glands of mice that had received radiation and mice that had received sham radiation. Tumors developed more quickly in mice that had been exposed to radiation; higher radiation doses were associated with increased tumor growth rates. Additionally, more of the tumors in irradiated mice were estrogen-receptor negative, a marker associated with aggressive breast cancer. By one year after transplantation, tumors had developed in all of the mice that had received radiation and in 69% of mice that had received sham radiation.

The team found that radiation led to the persistent activation of a protein called TGFβ, which is known to have a role in the response of tissues to radiation. Analyses showed that the radiation dose elicited a change in gene expression, most of which was dependent on the level of TGFβ. When the researchers irradiated mice in which TGFβ gene activity had been genetically reduced, the irradiation did not affect the frequency, latency or growth rate of estrogen-receptor–negative tumors. Put together, these data suggest that chronic TGFβ activity is the mechanism by which host irradiation accelerates mammary tumor growth in these mice. Further analysis revealed that radiation led to other molecular changes that were associated with the increased frequency of estrogen-receptor–negative tumors in mice exposed to radiation. These molecular changes were independent of the increased TGFβ gene activity associated with accelerated tumor growth.

Several features of the cancer in mice that had received radiation parallel those found in women with breast cancer who had received radiotherapy for childhood cancer. Such features include early onset cancer, a more aggressive tumor phenotype and markers associated with a worse prognosis. The authors conclude that the elevated cancer risk associated with radiation therapy potentially could be decreased by targeting host biology after radiation.