Authors:M. Akaboshi, Y. Tanaka, T. Sumino, J. Takada, and K. Kawai
The literature indicates that the interaction of Tb3+ with DNA modified by the antitumour drug cis-diaminedichloroplatinum(II) (CDDP) results in substantial enhancement of the
fluorescence of this cation, while no enhancement is observed in the case of DNA modified by irradiation with ionizing radiation.
This study investigates the effect of Tb3+ on the survival of cultured mammalian cells treated with CDDP. HeLa cells were treated with a combination of195mPt-CDDP and TbCl3, and the relationship between lethal effect and the numbers of Tb and/or Pt atoms binding to DNA, RNA and proteins was examined.
The Tb content in each fraction was determined using instrumental neutron activation analysis. It was found that the cytotoxic
effect of CDDP was greatly enhanced by the presence of Tb ions (D0 of CDDP fell from 8.3 μM without Tb to 3.2 μM with 0.75 mM Tb), while no such effect was found in radiation-induced cell-killing.
The number of Tb atoms bound to DNA molecules in a cell was calculated to be about 4.5·107, namely 1 per 1.400 nucleotides, under that situation.
Authors:M. Akaboshi, K. Kawai, Y. Tanaka, J. Takada, and T. Sumino
The effect of hyperthermia on the cell killing efficiency of Pt atoms binding to DNA, RNA and protein molecules of HeLa cells
treated withcis-diamine(1,1-cyclobutanedicarboxylato)platinum(II) (CBDCA) was examined. HeLa S-3 cells were treated with195mPt-radiolabeled CBDCA for 60 minutes at various temperatures, and the relationship between the lethal effect and the number
of Pt atoms binding to DNA, RNA and proteins was examined. The mean lethal concentration (D0) of carboplatin for a 60 min-treatment at 0, 25, 37, 40, 42 and 44°C was 671.2, 201.5, 67.3, 33.4, 20.2 and 15.6 μM, respectively.
By using identically treated cells, the number of Pt-atoms combined with DNA, RNA and protein molecules were determined in
the subcellular fractions. Thus, the D0's given as the drug concentrations were replaced with the number of Pt-atoms combined in each fraction. Then, the cell-killing
efficiency of the Pt atom was expressed as the reciprocal of the number of Pt-atoms combined and was calculated for each molecule.
The efficiency for DNA molecules was 0.699, 1.42, 2.65, 4.84, 7.74 and 8.28·104 nucleotides, respectively, for the conditions described above. From 0 to 44°C, the cell-killing efficiency of Pt atoms increased
by a factor of 11.9.
Authors:K. Kawai, Y. Tanaka, Y. Nakano, W. Ehrlich, and M. Akaboshi
An experimental method is described for the synthesis of195mPt-radiolabeled cis-diammine (glycolato) platinum (II) (254-S). Ten mg of 95% enriched194Pt was irradiated for 75 h in the hydraulic conveyer of KUR at a thermal neutron flux of ca. 8.15×1013 n·cm–2·s–1, and the195mPt-radiolabeled 254-S was synthesized and purified using HPLC (column: Dichrosorb Diol, elution: 80% CH3CN). The chemical yield was approximately 45%, with chemical purity greater than 98.4%. The radionuclidic purity was nearly 100% and the specific activity, 7.2 MBq·mg–1 254-S.
Authors:K. Kawai, H. Maki, W. Ehrlich, and M. Akaboshi
An improved method is described for the synthesis of195mPt-radiolabelled cis-diamminedichloroplatinum/II. An amount of 10 mg of 95% enriched194Pt was irradiated for 75 h in the hydraulic conveyer of the KUR at a thermal neutron flux of approximately 8.15×1013 n.cm–2.sec–1 and the195mPt-radiolabelled CDDP was purified using HPLC. The chemical yield is 61% its chemical purity is greater than 99.74% the radiochemical purity is nearly 100%, and the specific activity is 7.4×106 Bq mg–1 CDDP/200 Ci mg–1 CDDP/.
Authors:M. Akaboshi, T. Sumino, Y. Tanaka, J. Takada, K. Kawai, and K. Kawamoto
HeLa S-3 cells were treated with several rare earth elements, Ce, La, and Sm, at 37 °C for 1 hour and the relationship between the lethal effects of these elements and the number of the atoms bound to DNA, RNA, and proteins was examined. Among the 3 element, only Ce gave an exponential dose-survival relationship from which the value of mean lethal concentration (D0) was determined to be 6.75 mM. By using identically treated cells, the number of Ce atoms combined with DNA, RNA and protein molecules in HeLa cells were determined after fractionation of the cells using neutron activation analysis. In this way, theD0 value given as the Ce concentration was replaced by the number of Ce atoms combined with each fraction, then the target volumes, viz., cell killing efficiency, expressed as the reciprocal ofD0 value was calculated for each fraction. The results suggested that DNA and RNA could stochiometrically be the primary target molecule for cell killing by Ce.
Authors:Y. Tanaka, T. Sumino, K. Kawai, J. Takada, K. Kawamoto, and M. Akaboshi
The enhancement of cell-killing effect induced by60Co γ-rays on the aqueous solutions of potassium hexachloroplatinum(IV) (K2PtCl6) irradiated in the presence of various concentrations of NH4Cl was examined. HeLa S-3 cells were treated with the irradiated solutions for 60 minutes at 37°C, and cell survival was measured
by colony forming efficiency. The mean lethal concentration (D0) for the cells treated with non-irradiated K2PtCl6 solution (1 mg/ml) was 34.5 μl/ml. However, it decreased, namely the cell-killing effect of the solution increased with increasing
radiation dose up to 2.64·104 Gy in the case of 0.1M NH4Cl solution (in this condition, theD0 decreased to 9.6 μl/ml). No or only a slight enhancement was observed in the case of K2PtCl6 solutions irradiated in the presence of NaCl, (NH4)2HPO4, ammonium acetate or glycine. Observations using high performance liquid chromatography (HPLC) of irradiated K2PtCl6 solutions revealed the formation of cis- and/or trans-diaminedichloroplatinum (IV) (DDPs(IV)). However, the observed cell-killing
action of the solution was too high to be explained by the amount of both the DDPs(IV) formed by γ-rays.
Authors:T. Aze, M. Fujimura, H. Matsumura, K. Masumoto, N. Nakao, H. Matsuzaki, H. Nagai, and M. Kawai
In order to estimate the total radioactivity induced in a concrete shield by thermal neutron-capture reactions at high-energy
accelerator facilities, the observed activity of 36Cl in the concrete is expected to serve as an indicator of the thermal neutron fluence. Since 36Cl can also be produced from K and Ca by spallation reactions, we measured these production rates in order to clarify the
contribution of each reaction. The Cl, K, and Ca targets were irradiated with neutrons having a maximum energy of 500 MeV.
As a result, the production rates of 36Cl from Cl were only two orders higher than those from K and Ca. It was found that the 36Cl production ratios from Cl, K, and Ca were 6.7%, 6.8%, and 86.5%, respectively, and Ca was the main source of 36Cl production.
Authors:K. Kawai, S. Takada, Y. Nakano, W. Ehrlich, H. Maki, and M. Akaboshi
An experimental method is described for the synthesis of195mPt-radiolabeled (–)-(R)-2-aminomethylpyrrolidine (1,1-cyclobutanedicarboxylato)-2-platinum (II) (DWA2114R). An amount of 10 mg of 95% enriched194Pt was irradiated for 75 h in the hydraulic conveyer of the KUR at a thermal neutron flux of approximately 8.1×1013 n.cm–2.sec–1 and the195mPt-radiolabeled DWA2114R was purified using HPLC. The chemical yield is higher than 65%, its chemical purity is greater than 99.2%, the radiochemical purity is nearly 100%, and the specific activity is 6.7 MBq. mg–1 DWA2114R.
Authors:R. Suzuki, T. Ohdaira, K. Yamada, T. Yamazaki, N. Sei, T. Mikado, T. Noguchi, H. Ohgaki, S. Sugiyama, M. Chiwaki, T. Shimizu, M. Kawai, M. Yokoyama, S. Hamada, K. Saeki, N. Nishimura, and T. Tomimasu
A positron lifetime study has been done on dielectric multilayer cavity mirrors for free-electron-laser experiments by the use of a variable-energy pulsed positron beam. A long-lived ortho-positronium component has been observed at low positron energy region, corresponding to the depth of the top amorphous SiO2 layer. The intensity of the positronium component correlates with the degradation and restoration of the mirrors. We discuss the relation between the positronium intensity and degradation mechanism of the mirrors. The present studies revealed that the slow positron lifetime technique is highly sensitive to the properties of the mirrors and is useful for the evaluation of the mirrors.