BIOLOGICAL EFFECT OF PB-212 LOCALIZED IN THE NUCLEUS OF MAMMALIAN-CELLS - ROLE OF RECOIL ENERGY IN THE RADIOTOXICITY OF INTERNAL ALPHA-PARTICLE EMITTERS

The radiochemical dipyrrolidinedithiocarbamato-Pb-212 (II) [(212)pb(pDC)(2)] is synthesized and its effects on colony formation in cultured Chinese hamster V79 cells are investigated. The cellular uptake, biological retention, subcellular distribution and cytotoxicity of the radiocompound are determined. The (212)pb is taken up quickly by the cells, reaching saturation levels in 1.25 h. When the cells are washed, the intracellular activity is retained with a biological half-life of 11.6 h. Gamma-ray spectroscopy indicates that the Pb-212 daughters Bi-212, Po-212 and (208)T1) are in secular equilibrium within the cell. About 72% of the cellular activity localizes in the cell nucleus, of which 35% is bound specifically to nuclear DNA. The mean cellular uptake required to achieve 37% survival is 0.35 mBq of Pb-212 per cell, which delivers a dose of 1.0 Gy to the cell nucleus when the recoil energy of Bi-212 and Po-212 decays is ignored and 1.7 Gy when recoil is included. The corresponding RBE values compared to acute external Cs-137 gamma rays at 37% survival are 4.0 and 2.3, respectively. The chemical Pb(PDC)(2) is not chemotoxic at the concentrations used in this study. Because the beta-particle emitter Pb-212 decays to the alpha-particle-emitting daughters Bi-212 and Po-212, these studies provide information on the biological effects of alpha-particle decays that occur in the cell nucleus. Our earlier studies with cells of the same cell line using Po-210 (emits 5.3 MeV (alpha particle) localized predominantly in the cytoplasm resulted in an RBE of 6. These earlier results for Po-210, along with the present results for Pb-212, suggest that the recoil energy associated with the Bi-212 and Po-212 daughter nuclei plays little or no role in imparting biological damage to critical targets in the cell nucleus.