Biological effect of lead-212 localized in the nucleus of mammalian cells: role of recoil energy in the radiotoxicity of internal alpha-particle emitters.

The radiochemical dipyrrolidinedithiocarbamato-212Pb(II) [212Pb(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 212Pb 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 212Pb daughters (212Bi, 212Po and 208Tl) 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 212Pb per cell, which delivers a dose of 1.0 Gy to the cell nucleus when the recoil energy of 212Bi and 212Po decays is ignored and 1.7 Gy when recoil is included. The corresponding RBE values compared to acute external 137Cs 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 212Pb decays to the alpha-particle-emitting daughters 212Bi and 212Po, 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 210Po (emits 5.3 MeV alpha particle) localized predominantly in the cytoplasm resulted in an RBE of 6. These earlier results for 210Po, along with the present results for 212Pb, suggest that the recoil energy associated with the 212Bi and 212Po daughter nuclei plays little or no role in imparting biological damage to critical targets in the cell nucleus.