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.

The effect of surgical specimen-derived phosphorus and lead concentrations in non-small cell lung cancer patients on disease course

“…A recent study of the anti-cancer activity of phosphorus demonstrated that aqueous P is incorporated into nascent DNA. Through phosphorilization of the H2-AX histone, P disrupts the double helix, resulting in cytotoxicity which in turn increases apoptosis (10). In our study, phosphorus was found at higher concentrations in lung cancer tissue than in normal lung tissues, but at lower concentrations in deceased lung cancer patients than surviving patients.…”

“…One of the elements analyzed in this study was phosphorus, which is the second most abundant chemical element in the human body after calcium. In its inorganic form, phosphorus functions as a part of the structural framework of important biological molecules like RNA and DNA (10). In previous studies evaluating the various functions of phosphorus, mice were injected with human cancer cells as a model, and phosphorus was found to have anti-cancer activity (11)(12)(13).…”

Impact of Methods on the Measurement of mRNA Turnover

“…Thereafter, their use has declined for several reasons. First, radioactivity may elicit cellular damage, including DNA double-strand breaks [ 13 ], and may trigger cellular signaling that alters transcription and RNA stability. Second, the invention of qPCR and high-throughput RNA detection technologies paved the way for the spread of labelling with non-radioactively modified nucleotides so that the labelled RNA can be separated from the total RNA to be quantified.…”

Radiation Treatment in Women with Ovarian Cancer: Past, Present, and Future

“…In a colloidal suspension form, phosphorus-32 ( 32 P) forms a complex, insoluble particle, which can be injected directly into the peritoneal cavity. The colloidal suspension then prevents radioisotope from leaving the intended target and disseminating throughout the body ( 11 , 12 ). The first reported clinical application of 32 P was in the 1930s and other intraperitoneal radioactive isotypes were investigated in the 1950s and 1960s most notably 198 Au, but for reasons of safety and toxicity, 32 P became the agent of choice for the treatment of ovarian cancer and the palliation of malignant ascites in the 1960s ( 12 , 13 ).…”