TY  - JOUR
A1  - Smirnov, Denis A.
A1  - Brady, Lauren
A1  - Halasa, Krzysztof
A1  - Morley, Michael
A1  - Solomon, Sonia
A1  - Cheung, Vivian G.
T1  - Genetic variation in radiation-induced cell death
Y1  - 2012/02/01 
JF  - Genome Research 
JO  - Genome Research 
SP  - 332 
EP  - 339 
DO  - 10.1101/gr.122044.111 
VL  - 22 
IS  - 2 
UR  - http://genome.cshlp.org/content/22/2/332.abstract 
N2  - Radiation exposure through environmental, medical, and occupational settings is increasingly common. While radiation has harmful effects, it has utility in many applications such as radiotherapy for cancer. To increase the efficacy of radiation treatment and minimize its risks, a better understanding of the individual differences in radiosensitivity and the molecular basis of radiation response is needed. Here, we integrated human genetic and functional genomic approaches to study the response of human cells to radiation. We measured radiation-induced changes in gene expression and cell death in B cells from normal individuals. We found extensive individual variation in gene expression and cellular responses. To understand the genetic basis of this variation, we mapped the DNA sequence variants that influence expression response to radiation. We also identified radiation-responsive genes that regulate cell death; silencing of these genes by small interfering RNA led to an increase in radiation-induced cell death in human B cells, colorectal and prostate cancer cells. Together these results uncovered DNA variants that contribute to radiosensitivity and identified genes that can be targeted to increase the sensitivity of tumors to radiation. 
ER  -