Previous studies in our laboratory have sought to determine if metabolites in the urine of mice receiving non-lethal whole body radiation could predict for radiation-induced cancer induction prior to the observation of tumor mass. We have analyzed 106 urine metabolites acquired from 100 mice over a two year period (n = 25 0 Gy control; n = 75 5.4 Gy). Tumor pathology was determined for each mouse. Principle component analysis (PCA) using over 7000 metabolites revealed that the metabolite profile of control animals can be clearly separated from radiation exposed animals as early as 3 months post-TBI that predict for tumor induction. Further, the alteration in urine metabolites in irradiated mice could distinguish between hematopoietic and solid tumors. Lastly, the urine metabolite profile of TBI treated mice at 6 months of age more resemble the profile of aged control mice (18 months of age). We are currently repeating this study with a focus on identifying the chemical structure of metabolites predictive of radiation-induced cancer. We are currently evaluating data from this study. Changes in urine metabolite profiles following radiation may provide a means to predict for radiation-induced cancer induction. We are also exploring the influence of the gut microflora on radiation-induced carcinogenesis. The animal's gut microflora composition is modulated by use of an antibiotic cocktail in the drinking water prior to whole body radiation. The study is currently ongoing. Lastly, we have initiated a life span study in mice exposed to non-lethal 3 Gy whole body radiation with and without rapamycin in their chow. Rapamycin has been shown to increase the life span of mice and decrease carcinogenesis. Further, rapamycin inhibits radiation-induced senescence. Whether or not tissue senescence is important in carcinogenesis is a topic of much interest in our laboratory.
| Cook, John A; Naz, Sarwat; Anver, Miriam R et al. (2018) Cancer Incidence in C3H Mice Protected from Lethal Total-Body Radiation after Amifostine. Radiat Res 189:490-496 |
| Ueno, Megumi; Matsumoto, Shingo; Matsumoto, Atsuko et al. (2017) Effect of amifostine, a radiation-protecting drug, on oxygen concentration in tissue measured by EPR oximetry and imaging. J Clin Biochem Nutr 60:151-155 |
| Cook, John A; Chandramouli, Gadisetti V R; Anver, Miriam R et al. (2016) Mass Spectrometry-Based Metabolomics Identifies Longitudinal Urinary Metabolite Profiles Predictive of Radiation-Induced Cancer. Cancer Res 76:1569-77 |
| Mitchell, James B; Anver, Miriam R; Sowers, Anastasia L et al. (2012) The antioxidant tempol reduces carcinogenesis and enhances survival in mice when administered after nonlethal total body radiation. Cancer Res 72:4846-55 |
