Previous studies in our laboratory have sought to determine if metabolites in the urine of mice receiving non-lethal total-body radiation (TBI) 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 successfully repeated this study and are currently focusing 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 might provide a means to predict for radiation-induced cancer induction. We have finished a study exploring the influence of the gut microflora on radiation-induced carcinogenesis. The animal's gut microflora composition was modulated by use of an antibiotic cocktail in the drinking water prior to whole body radiation. We found that reducing the gut microflora 3 weeks before TBI 3 weeks after shortened the lifespan of mice compared to TBI alone, implicating the importance of the gut microflora in radiation-induced carcinogenesis. We finished this year a life span study in mice exposed to non-lethal 3 Gy TBI with and without rapamycin in their chow. Rapamycin treatment extended the life span of mice compared to TBI alone by decreasing the induction of hepatocellular carcinomas. We are currently analyzing this data. Lastly, we have demonstrated that the FDA approved radioprotector, Amifostine protects against radiation-induced carcinogenesis; however, mice pre-treated with Amifostine before TBI exhibited less hematopoietic neoplasms than a comparable control group and higher incidences of solid neoplasms. This finding was published and we are continuing studies related to the mechanism of this finding.
| 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 |
