Phosphorus-32, a clinically available drug, inhibits cancer growth by inducing DNA double-strand breakage

PLoS One. 2015 Jun 1;10(6):e0128152. doi: 10.1371/journal.pone.0128152. eCollection 2015.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Beta Particles / therapeutic use
  • Cell Proliferation / radiation effects
  • DNA Breaks, Double-Stranded / radiation effects*
  • HeLa Cells
  • Humans
  • Injections, Intravenous
  • Mice
  • Models, Molecular
  • Nucleic Acid Conformation
  • Phosphorus Radioisotopes / administration & dosage
  • Phosphorus Radioisotopes / chemistry
  • Phosphorus Radioisotopes / therapeutic use*
  • Time Factors
  • Water / chemistry

Substances

  • Phosphorus Radioisotopes
  • Water