Phosphorus-32, a Clinically Available Drug, Inhibits Cancer Growth by Inducing DNA Double-Strand Breakage

Radioisotopes that emit electrons (beta particles), such as radioiodine, can effectively kill target cells, including cancer cells. Aqueous (32)P[PO(4)] is a pure beta-emitter that has been used for several decades to treat non-malignant human myeloproliferative diseases. (32)P[PO(4)] was directly compared to a more powerful pure beta-emitter, the clinically important (90)Y isotope. In vitro, (32)P[PO(4)] was more effective at killing cells than was the more powerful isotope (90)Y (P ≤ 0.001) and also caused substantially more double-stranded DNA breaks than did (90)Y. In vivo, a single low-dose intravenous dose of aqueous elemental (32)P 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. (32)P[PO(4)] should be considered for human clinical trials as a potential novel anti-cancer drug.