The Impact of External Beam Radiation Therapy on Oxidative Damage in the Transgenic Adenocarcinoma of the Mouse Prostate (TRAMP) Prostate Cancer Model (P05-022-19)

Abstract

ObjectivesExternal beam radiation therapy (EBRT) is one of the most common treatments for primary prostate cancer. The primary limitation for EBRT is the potential for damage to surrounding tissues. Epidemiological evidence indicates that tomato products are associated with reduced PCa progression. Tomatoes contain carotenoids and other potent antioxidants that may protect the surrounding tissue from the detrimental effects of EBRT. The objective of this pilot study is to determine if tomato feeding can alter early inflammatory and oxidative events following a single dose of radiation that may predict a more successful therapeutic outcome. MethodsTo test this hypothesis, male TRAMP mice (n = 60) were provided a powdered AIN-93 G diet (Control) or an AIN-93 G diet modified to contain 10% lyophilized tomato paste (TP; n = 30) beginning at 4 weeks of age. Mice were monitored by ultrasound biweekly for in vivo tumor detection and 3-D volumetric growth measurement. Tumors were irradiated with 7.5 gy (n = 15 per diet) or 0 gy (sham, n = 15 per diet) of radiation by a Cobolt-60 source once the animal had a 1000 mm3 tumor. Animals were euthanized after 24 hours and carotenoids were measured by high performance liquid chromatography (HPLC) in the tumor and liver. Sections of tumor, liver, kidneys, bladder, lymph, bladder and intestines were stained by hematoxylin and eosin-stained (H&E) and were assessed for tumor grade and inflammatory markers. Pro-inflammatory cytokines (IL-6 and TNFα) will be measured from the serum and tumor tissues by ELISA. Oxidative damage will be analyzed through the γH2AX assay and through measurement of reduced glutathione. ResultsThis study will be the first to explore the effects of tomato powder on the PCa tumor microenvironment following irradiation. We hypothesize that lifelong tomato consumption will delay tumor growth; will protect surrounding tissues from inflammatory and oxidative damage (reducing circulating pro-inflammatory cytokines); and will reduce histopathological markers of inflammation in surrounding tissues following a single exposure to 60-CO radiation in the TRAMP model. ConclusionsThis study will provide important preclinical data to inform future clinical trials that may positively affect dietary recommendations for EBRT to improve therapeutic outcomes. Funding SourcesUniversity of Illinois at Urbana-Champaign.