Ionizing Radiation Exposure Stimulates Expression of Clusterin

The Science

What happens when ionizing radiation passes through biological tissues? DOE researchers at the University of Texas Southwestern Medical Center at Dallas and the Indiana University Simon Cancer Center have shown that low doses of ionizing radiation of 10 cGy or less (about 2–3 times the annual exposure limit for DOE workers) stimulates induction of an extracellular protein, secretory clusterin (sCLU), that clears cell debris and increases cell survival in response to damage. sCLU levels are elevated in various tissues after low-dose radiation exposure and are permanently elevated in many early-stage cancers. The researchers also showed, for the first time, that sCLU expression is related to genomic instability induced by low-dose radiation and in cells with spontaneous genomic instability. The hypothesis tested was that normal cells induce sCLU in a transient manner, whereas persistent damage caused by permanent genomic instability leads to constitutive sCLU expression. The scientists found that up regulation of the sCLU signaling cascade may be an important pro-survival response pathway following radiation exposure as well as in response to constitutive damage induced through genetic instability. The results appeared in the advance online publication of the cancer journal, Oncogene. These findings add important clues to our understanding of radiation responses in normal tissues.

BER Program Manager

Resham Kulkarni

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

References

Goetz, E. M., B. Shankar, Y. Zou, J. C. Morales, X. Luo, S. Araki, R. Bachoo, L. D. Mayo, and D. A. Boothman. 2011. “ATM-Dependent IGF-1 Induction Regulates Secretory Clusterin Expression After DNA Damage and in Genetic Instability,” Oncogene. DOI:10.1038/onc.2011.92.