title: Phosphorus-32, a clinically available drug, inhibits cancer growth by inducing DNA double-strand breakage.
abstract: Radioisotopes that emit electrons (beta particles), such as radioiodine, can effectively kill target cells, including cancer cells. Aqueous 32P[PO4] is a pure beta-emitter that has been used for several decades to treat non-malignant human myeloproliferative diseases. 32P[PO4] was directly compared to a more powerful pure beta-emitter, the clinically important 90Y isotope. In vitro, 32P[PO4] was more effective at killing cells than was the more powerful isotope 90Y (P ≤ 0.001) and also caused substantially more double-stranded DNA breaks than did 90Y. In vivo, a single low-dose intravenous dose of aqueous elemental 32P significantly inhibited tumor growth in the syngeneic murine cancer model (P ≤ 0.001). This effect is exerted by direct incorporation into nascent DNA chains, resulting in double-stranded breakage, a unique mechanism not duplicatable by other, more powerful electron-emitting radioisotopes. 32P[PO4] should be considered for human clinical trials as a potential novel anti-cancer drug.
authors.affiliation: Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.
authors.forename: Yulan
authors.initials: Y
authors.lastname: Cheng
authors.affiliation: Department of Radiation Oncology and Molecular Radiation, The Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Ana P
authors.initials: AP
authors.lastname: Kiess
authors.affiliation: Department of Radiation Oncology and Molecular Radiation, The Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Herman
authors.affiliation: Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.
authors.forename: Martin G
authors.initials: MG
authors.lastname: Pomper
authors.affiliation: Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Meltzer
authors.affiliation: Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.
authors.forename: John M
authors.initials: JM
authors.lastname: Abraham
mesh_terms: D000818:Animals; D001610:Beta Particles / Q000627:therapeutic use; D049109:Cell Proliferation / Q000528:radiation effects; D053903:DNA Breaks, Double-Stranded / Q000528:radiation effects*; D006367:HeLa Cells; D006801:Humans; D007275:Injections, Intravenous; D051379:Mice; D008958:Models, Molecular; D009690:Nucleic Acid Conformation; D010761:Phosphorus Radioisotopes / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use*; D013997:Time Factors; D014867:Water / Q000737:chemistry
chemical_list: D010761:Phosphorus Radioisotopes; D014867:Water