The effects of radon daughter α-particle irradiation in K1 and xrs-5 CHO cell lines

Shadley, Jeff D.; Whitlock, Jenny L.; Rotmensch, Jacob; Atcher, Robert W.; Tang, Jian; Schwartz, Jeffrey L.

doi:10.1016/0027-5107(91)90089-7

Cited by 34 publications

(14 citation statements)

References 38 publications

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“…Given that 98.2% of the testicular absorbed dose is delivered by 212 Bi and its subsequent daughters, while only 1.8% of the dose is from the parent 212 Pb (see Testicular Absorbed Dose section above), it is not unreasonable to compare our results with those obtained for 212 Bi by Shadley et al (43). They irradiated CHO K1 cells in vitro with 212 Bi localized extracellularly in the culture medium which resulted in a polyenergetic α-particle field similar to that encountered in the testis.…”

Section: Rbe Of 212 Pb In Equilibrium With Daughterscontrasting

confidence: 35%

Relative Biological Effectiveness of Alpha-Particle Emitters In Vivo at Low Doses

Howell¹,

Azure²,

Narra³

et al. 1994

Radiation Research

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The therapeutic potential of radionuclides that emit α particles, as well as their associated health hazards, have attracted considerable attention. The 224 Ra daughters 212 Pb and 212 Bi, by virtue of their radiation properties which involve emission of α and β particles in their decay to stable 208 Pb, have been proposed as candidates for radioimmunotherapy. Using mouse testes as the experimental model and testicular spermhead survival as the biological end point, the present work examines the radiotoxicity of 212 Pb and its daughters. When 212 Pb, in equilibrium with its daughters 212 Bi, 212 Po and 208 Tl, was administered directly into the testis, the dose required to achieve 37% survival (D 37 ) was 0.143 ± 0.014 Gy and the corresponding RBE of the mixed radiation field was 4.7 when compared to the D 37 for acute external 120 kVp X rays. This datum, in conjunction with our earlier results for 210 Po, was used to obtain an RBE-LET relationship for α particles emitted by tissue-incorporated radionuclides: RBE α = 4.8 − 6.1 × 10 −2 LET + 1.0 × 10 −3 LET 2 . Similarly, the dependence of RBE on α-particle energy E α was given by . These relationships, based on in vivo experimental data, may be valuable in predicting biological effects of α-particle emitters.

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Section: Rbe Of 212 Pb In Equilibrium With Daughterscontrasting

confidence: 35%

Relative Biological Effectiveness of Alpha-Particle Emitters In Vivo at Low Doses

Howell¹,

Azure²,

Narra³

et al. 1994

Radiation Research

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“…Comparatively less experimental data where RBE values are clearly delineated are available on the effects of tissue-incorporated α-particle emitters (4). A number of studies have been published recently using in vitro techniques where the radionuclides were located in the culture medium, thereby irradiating the cells with a spectrum of α-particle energies (5)(6)(7)(8)(9)(10). Other studies have been performed both in vitro and in vivo to elucidate the RBE of α-particle emitters specifically incorporated into cells (10)(11)(12)(13)(14)(15).…”

Section: Introductionmentioning

confidence: 99%

Biological Effect of Lead-212 Localized in the Nucleus of Mammalian Cells: Role of Recoil Energy in the Radiotoxicity of Internal Alpha-Particle Emitters

Azure¹,

Archer²,

Sastry³

et al. 1994

Radiation Research

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

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“…Previously, we reported on the radiation sensitivity of CHO-KI cells and mutation induction in this cell line following exposure to X rays and a particles (16). In the present study, we have chosen doses of 'y rays (6 Gy) and a particles (2 Gy (Table 2).…”

Section: Cho-ki Cells and Xrs-5 Cellsmentioning

confidence: 99%

“…Independent spontaneous hprt-deficient mutants were isolated according to our established protocol (11,16). Briefly, cells were treated with HAT medium (medium F12FCM5 supplemented with 10-4 M hypoxanthine, 10-6 M aminopterin, and 10-5 M thymidine) for 5 days to eliminate preexisting mutants.…”

Section: Spontaneous Hprt Mutantsmentioning

confidence: 99%

“…Cells were exposed to 212Bi chelated to diethylene triamine pentaacetic acid (212Bi-DTPA) to prevent attachment of 212Bi to the cells and to keep the activity extracellular. Radioactivity was assayed using a calibrated 3 x 3-in Nal well detector and dose was calculated as described (16,18,19 into 150-cm2 flasks and maintained as exponentially growing populations for 8 to 10 days, the previously determined optimum phenotypic expression time for the hprt locus. Mutant frequency was determined by scoring for resistance to 6-thioguanine.…”

Section: Radiaton Mutagenesismentioning

confidence: 99%

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Molecular Markers of Ionizing Radiation-Induced Gene Mutations in Mammalian Cells

Hsie¹,

Porter²,

Xu³

et al. 1996

Environmental Health Perspectives

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We have isolated independent Chinese hamster ovary (CHO) cell mutants at the hypoxanthine guanine phosphoribosyltransferase (hprt) locus from untreated, 60Co y-ray-exposed, and 212Bi a-exposed cells and identified the molecular changes underlying the mutation determined by multiplex polymerase chain reaction (PCR)-based exon deletion analysis. Both the parental CHO-Kl cells and the X-ray-sensitive mutant xrs-5 cells were studied. The radiosensitive xrs-5 cells are defective in DNA double-strand break rejoining ability and in V(D)J recombination, which can be complemented by Ku protein. Of the 71 spontaneous CHO-Kl hprt mutants analyzed, 78% showed no change in exon number or size, 20% showed loss of one to eight exons (partial deletion), and 3% showed loss of all nine hprt exons (total deletion). Exposure of CHO-Kl cells to 6 Gy of y rays, which reduced survival levels to 10%, produced a high deletion spectrum with 45% of the 20 mutants analyzed showing a loss of one to eight exons and 30% showing total deletion. Exposure to an equitoxic dose of cx radiation from 212Bi, a 220Rn daughter, resulted in a spectrum similar to the tray spectrum in that 75% of the 49 mutants analyzed were deletions. The cx radiation, however, tended to produce larger intragenic deletions than y radiation. Of the 92 spontaneous xrs-5 mutants analyzed for deletions, 43% showed a loss of one to eight exons and 14% showed total deletion. This suggests that, in certain regions of the hprt gene, base alterations can be converted into large deletions and alteration in the Ku protein complex can influence this type of mutational process. Exposure to ax radiation (10% survival) to xrs-5 cells resulted in a deletion spectrum similar to that seen in CHO-Kl cells. Of the 49 mutants analyzed, 43% showed no change in exon number or size, 16% showed a loss of one to eight exons, and 41 % showed total deletion. While the defect in xrs-5 cells has a profound effect on spontaneous mutant spectra, this defect does not appear to affect a-induced mutation spectra. EnvironHealth Perspect 104(Suppl 3): 675-678 (1996)

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The effects of radon daughter α-particle irradiation in K1 and xrs-5 CHO cell lines

Cited by 34 publications

References 38 publications

Relative Biological Effectiveness of Alpha-Particle Emitters In Vivo at Low Doses

Relative Biological Effectiveness of Alpha-Particle Emitters In Vivo at Low Doses

Biological Effect of Lead-212 Localized in the Nucleus of Mammalian Cells: Role of Recoil Energy in the Radiotoxicity of Internal Alpha-Particle Emitters

Molecular Markers of Ionizing Radiation-Induced Gene Mutations in Mammalian Cells

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