Radiation is a Complex Carcinogen

The Science

How is cancer caused by ionizing radiation? A new study by DOE researchers challenges the notion that DNA damage is the sole action of radiation as a carcinogen. A small piece of tumor was transplanted into irradiated mice to determine if radiation exposure of the surrounding host tissue would affect the growth of the resulting tumor. The group identified two distinct carcinogenic mechanisms mediated by the surrounding host tissue. One mechanism affected tumor latency—tumors grew more quickly in irradiated vs. unirradiated mice. The second mechanism influenced the specific type of cancer produced—tumors in the irradiated mice were much more likely to be estrogen receptor negative. These data reinforce the concept that signals from surrounding irradiated cells can promote the process of carcinogenesis. Unlike initial DNA damage, radiation effects originating from the surrounding cell microenvironment develop in a non-linear fashion with respect to dose, underscoring the complexity of the biological effect.


Tissue microenvironment is an important determinant of carcinogenesis. Researchers demonstrate that ionizing radiation, a known carcinogen, affects cancer frequency and characteristics by acting on the microenvironment. Using a mammary chimera model in which an irradiated host is transplanted with oncogenic Trp53 null epithelium, the reserach team show accelerated development of aggressive tumors whose molecular signatures were distinct from tumors arising in nonirradiated hosts. Molecular and genetic approaches show that TGFβ mediated tumor acceleration. Tumor molecular signatures implicated TGFβ, and genetically reducing TGFβ abrogated the effect on latency.

Principal Investigator

Mary Helen Barcellos-Hoff
New York University

BER Program Manager

Resham Kulkarni

U.S. Department of Energy, Biological and Environmental Research (SC-33)
Biological Systems Science Division
[email protected]


Nguyen, D. H., H. A. Oketch-Rabah, I. Illa-Bochaca, F. C. Geyer, J. S. Reis-Filho, J-H. Maco, S. A. Ravani, J. Zavadil, A. D. Borowsky, D. J. Jerry, K. A. Dunphy, J. H. Seo, S. Haslam, D. Medina, and M. H. Barcellos-Hoff. 2011. “Radiation Acts on the Microenvironment To Affect Breast Carcinogenesis by Distinct Mechanisms that Decrease Cancer Latency and Affect Tumor Type,” Cancer Cell 19, 640–651. DOI:10.1016/j.ccr.2011.03.011.