Journal
LIFE SCIENCES IN SPACE RESEARCH
Volume 19, Issue -, Pages 31-42Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.lssr.2018.08.002
Keywords
Ionizing radiation; Bragg peak; Lung cancer; Persistent DNA damage; Adenocarcinoma
Funding
- NASA [NNX16AE08G, NNX15AI21G]
- Cancer Training Grant [T32CA124334]
- NIH [C06 RR30414]
- Harold Simmons NCI Designated Comprehensive Cancer Center Support Grant [CA142543]
- NASA [NNX16AE08G, 906041] Funding Source: Federal RePORTER
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There are considerable health risks related to ionizing and proton radiation exposure. While there is a long history of health risks associated with ionizing (photon) radiation exposure, there is a limited understanding of the long-term health risks associated with proton radiation exposure. Since proton radiation is becoming more common in cancer therapy, the long-term biological effects of proton radiation remain less well characterized in terms of radiotherapy and well as for astronauts during deep space explorations. In this study, we compared the long-term side effects of proton radiation to equivalent doses of X-rays in the initiation and progression of premalignant lesions in a lung cancer susceptible mouse model (K-ras(LA1)). We show proton irradiation causes more complex DNA damage that is not completely repaired resulting in increased oxidative stress in the lungs both acutely and persistently. We further observed K-ras(LA1) mice irradiated with protons had an increased number and size of initiated and premalignant lesions and adenomas that were often infiltrated with inflammatory cells. Proton irradiated mice had a lower median survival and increased carcinoma incidence as compared to unirradiated controls and X-rays exposed mice. Our conclusion is that exposure to proton irradiation enhances the progression of premalignant lesions to invasive carcinomas through persistent DNA damage, chronic oxidative stress, and immunosuppression.
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