Proton radiation-induced cancer progression.

Abstract

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-rasLA1). 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-rasLA1 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.

• Authors: Krishna Luitel, Ronald Bozeman, Aadil Kaisani, Sang Bum Kim, Summer Barron, James A Richardson, Jerry W Shay
• Journal: Life sciences in space research (Life Sci Space Res (Amst)) Vol. 19 Pg. 31-42 (Nov 2018) ISSN: 2214-5532 [Electronic] Netherlands
• PMID: 30482279 (Publication Type: Journal Article)
• Copyright: Copyright © 2018 The Committee on Space Research (COSPAR). Published by Elsevier Ltd. All rights reserved.

Chemical References

• Protons
• Malondialdehyde

Topics

• Animals
• DNA Damage
• Disease Models, Animal
• Disease Progression
• Dose-Response Relationship, Radiation
• Female
• Humans
• Inflammation (etiology, metabolism, pathology)
• Lung Neoplasms (etiology, metabolism, pathology)
• Male
• Malondialdehyde (metabolism)
• Mice
• Neoplasm Invasiveness
• Neoplasms, Radiation-Induced (etiology, metabolism, pathology)
• Oxidative Stress
• Protons (adverse effects)