Effects of Low-dose Gamma Radiation in a Murine Model of Benzo[a]pyrene-induced Lung Cancer
Year: 2015
Type: article
Abstract: Lung cancer is the leading cause of cancer related mortality in the United States and in the world. One of the carcinogenic compounds found in cigarette smoke, Benzo[a]pyrene (B[a]P), at high levels elicits a number of inflammatory events consistent with those found in lung cancer patients. In our studies, the effects of low-dose gamma radiation (LDR) on carcinogenesis and tumor progression in a murine model of B[a]P-induced lung cancer were investigated. Two studies (46 weeks in duration) were conducted to assess the effects of fractionated doses of low-dose gamma rays on whole body irradiated A/J mice either before or following intraperitoneal injection with the carcinogen. Additionally, a series of short-term studies were performed to investigate the effects of LDR and B[a]P on Kras mutation in tumors, leukocyte cytotoxicity and function, and oxidative stress in mice. Treatment with fractionated doses of LDR (100 mGy) delivered post B[a]P injection suppressed carcinogen-induced lung adenoma formation and prevented the multiplicity of these tumors, however exposure to LDR delivered prophylactically failed to prevent B[a]P-induced carcinogenesis or tumor progression. Radiation alone did not induce lung tumors in either study. B[a]P was cytotoxic to leukocytes and promoted inflammation through pro-inflammatory cytokine secretion (IL-β, IL-6, IL-17, TNF-α), infiltration of inflammatory cells, and increased lipid peroxidation in lungs and spleens of mice. LDR increased anti-inflammatory cytokine secretion (IL-2, IL-4, IL-10) in the spleen but this did not mitigate the inflammatory response induced by B[a]P. In addition we found no evidence that LDR reduces B[a]P-mediated lipid peroxidation in either spleen or lung. We also observed no change in Kras mutation incidence between treatment groups. Therefore we believe that it is unlikely that LDR suppresses B[a]P-mediated tumor progression through modulating Kras mutation, the immune response, or by reducing oxidative stress. Herein we have demonstrated that exposure to radiation at low doses does not increase cancer risk and suppresses the progression of lung cancer when delivered as a treatment. Our studies support the continued research of LDR in animal models to identify the mechanisms behind its ability to inhibit cancer progression for the potential use of LDR in human treatment of cancer in the future.
Author: Veronica R. Bruce
Language: English
Subfield: Radiology, Nuclear Medicine and Imaging
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W1894242714