title: A low-dose arsenic-induced p53 protein-mediated metabolic mechanism of radiotherapy protection.
abstract: Radiotherapy is the current frontline cancer treatment, but the resulting severe side effects often pose a significant threat to cancer patients, raising a pressing need for the development of effective strategies for radiotherapy protection. We exploited the distinct metabolic characteristics between normal and malignant cells for a metabolic mechanism of normal tissue protection. We showed that low doses of arsenic induce HIF-1α, which activates a metabolic shift from oxidative phosphorylation to glycolysis, resulting in increased cellular resistance to radiation. Of importance is that low-dose arsenic-induced HIF-1α requires functional p53, limiting the glycolytic shift to normal cells. Using tumor-bearing mice, we provide proof of principle for selective normal tissue protection against radiation injury.
authors.affiliation: From the Department of Genetics and Complex Diseases, Harvard School of Public Health, Boston, Massachusetts 02115 and.
authors.forename: Suthakar
authors.initials: S
authors.lastname: Ganapathy
authors.forename: Shaowen
authors.initials: S
authors.lastname: Xiao
authors.forename: Mei
authors.initials: M
authors.lastname: Yang
authors.forename: Min
authors.initials: M
authors.lastname: Qi
authors.forename: Doo Eun
authors.initials: DE
authors.lastname: Choi
authors.forename: Chul S
authors.initials: CS
authors.lastname: Ha
authors.forename: John B
authors.initials: JB
authors.lastname: Little
authors.forename: Zhi-Min
authors.initials: ZM
authors.lastname: Yuan
mesh_terms: D000818:Animals; D001151:Arsenic / Q000494:pharmacology*; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D006019:Glycolysis / Q000187:drug effects / Q000528:radiation effects; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D008660:Metabolism / Q000187:drug effects* / Q000528:radiation effects; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D016328:NF-kappa B / Q000378:metabolism; D011836:Radiation Tolerance / Q000187:drug effects / Q000528:radiation effects; D011837:Radiation-Protective Agents / Q000494:pharmacology*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D014916:Whole-Body Irradiation
chemical_list: D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D016328:NF-kappa B; D011837:Radiation-Protective Agents; D016159:Tumor Suppressor Protein p53; D001151:Arsenic
keywords: DNA Damage; Glycolysis; Metabolism; Signal Transduction; p53