A >20-fold increase in X-ray computed tomography (CT) use during the last 30 years has caused considerable concern because of the potential carcinogenic risk from these CT exposures. Estimating the carcinogenic risk from high-energy, single high-dose exposures obtained from atomic bomb survivors and extrapolating these data to multiple low-energy, low-dose CT exposures using the Linear No-Threshold (LNT) model may not give an accurate assessment of actual cancer risk. Recently, the National Lung Cancer Screening Trial (NLST) reported that annual CT scans of current and former heavy smokers reduced lung cancer mortality by 20%, highlighting the need to better define the carcinogenic risk associated with these annual CT screening exposures. In this study, we used the bitransgenic CCSP-rtTA/Ki-ras mouse model that conditionally expresses the human mutant Ki-rasG12C gene in a doxycycline-inducible and lung-specific manner to measure the carcinogenic risk of exposure to multiple whole-body CT doses that approximate the annual NLST screening protocol. Irradiated mice expressing the Ki-rasG12C gene in their lungs had a significant (P = 0.01) 43% increase in the number of tumors/mouse (24.1 ± 1.9) compared to unirradiated mice (16.8 ± 1.3). Irradiated females had significantly (P < 0.005) more excess tumors than irradiated males. No tumor size difference or dose response was observed over the total dose range of 80–160 mGy for either sex. Irradiated bitransgenic mice that did not express the Ki-rasG12C gene had a low tumor incidence (≤0.1/mouse) that was not affected by exposure to CT radiation. These results suggest that (i) estimating the carcinogenic risk of multiple CT exposures from high-dose carcinogenesis data using the LNT model may be inappropriate for current and former smokers and (ii) any increased carcinogenic risk after exposure to fractionated low-dose CT-radiation may be restricted to only those individuals expressing cancer susceptibility genes in their tissues at the time of exposure.
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1 December 2011
SHORT COMMUNICATION|
September 30 2011
Cancer-Prone Mice Expressing the Ki-rasG12C Gene Show Increased Lung Carcinogenesis after CT Screening Exposures Available to Purchase
Michael T. Munley;
Michael T. Munley
1
a Department of Radiation Oncology, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, North Carolina 27157
g Comprehensive Cancer Center of Wake Forest University, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, North Carolina 27157
1 Address for correspondence: Department of Radiation Oncology, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157; e-mail: [email protected].
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Joseph E. Moore;
Joseph E. Moore
b Department of Cancer Biology, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, North Carolina 27157
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Matthew C. Walb;
Matthew C. Walb
a Department of Radiation Oncology, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, North Carolina 27157
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Scott P. Isom;
Scott P. Isom
c Department of Public Health Sciences, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, North Carolina 27157
g Comprehensive Cancer Center of Wake Forest University, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, North Carolina 27157
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John D. Olson;
John D. Olson
d Department of Center for Biomolecular Imaging, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, North Carolina 27157
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J. Gregory Zora;
J. Gregory Zora
b Department of Cancer Biology, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, North Carolina 27157
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Nancy D. Kock;
Nancy D. Kock
e Department of Pathology, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, North Carolina 27157
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Kenneth T. Wheeler;
Kenneth T. Wheeler
f Department of Radiology, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, North Carolina 27157
g Comprehensive Cancer Center of Wake Forest University, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, North Carolina 27157
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Mark Steven Miller
Mark Steven Miller
b Department of Cancer Biology, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, North Carolina 27157
g Comprehensive Cancer Center of Wake Forest University, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, North Carolina 27157
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Radiat Res (2011) 176 (6): 842–848.
Article history
Received:
April 26 2011
Accepted:
September 05 2011
Citation
Michael T. Munley, Joseph E. Moore, Matthew C. Walb, Scott P. Isom, John D. Olson, J. Gregory Zora, Nancy D. Kock, Kenneth T. Wheeler, Mark Steven Miller; Cancer-Prone Mice Expressing the Ki-rasG12C Gene Show Increased Lung Carcinogenesis after CT Screening Exposures. Radiat Res 1 December 2011; 176 (6): 842–848. doi: https://doi.org/10.1667/RR2649.1
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