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Biomedical subjects

Y Ujeno

Publications and source records attributed to Y Ujeno.

17 recordsLinked to original sources

Binding characteristics of (-)-(R)-2-aminomethylpyrrolidine(1,1-cyclobutanedicarboxylato)-2-platin um(II) to DNA, RNA and protein molecules in HeLa cells and its lethal effect: comparison with cis- and trans-diamminedichloroplatinums(II).

HeLa S-3 cells were treated with 195mPt-radiolabeled (-)-(R)-2-aminomethylpyrrolidine(1,1-cyclobutanedicarboxylato++ +)-2-platinum(II) (DWA2114R) under various conditions, and the relationship between the lethal effect of the agent and the number of platinum (Pt) atoms binding to DNA, RNA and proteins was examined. The values of mean lethal concentration for the cells treated with DWA2114 at 37 degrees C for 1, 2 and 3 h were 137.3, 75.10 and 51.17 microM, respectively. Cells were treated identically and the numbers of Pt atoms combined with DNA, RNA and protein molecules were determined after fractionation of the cells. In this way, the D0 values (D0, dose that would give an average of one lethal event per member of the population), expressed as the drug concentration, were substituted for the number of Pt atoms combined with each fraction. The target volumes, the efficacy of Pt atom to kill cells expressed as the reciprocals of the D0 values, were then calculated for each fraction. Our findings suggested that DNA was the primary target molecule for cell killing by DWA2114R. The target volumes for DNA were 3.36 x 10(4), 4.00 x 10(4) and 4.10 x 10(4) nucleotides for 1-, 2- and 3-h treated cells, respectively. The cell-killing effects of DWA2114R were lower than those of cis-diamminedichloroplatinum(II) (CDDP) by factors of 1.54, 1.42 and 2.51 for 1-, 2- and 3-h treatments at 37 degrees C, respectively, in terms of the target volume, while those in terms of the mean lethal dose (D0) were 14.8, 11.2 and 16.0, respectively. The efficacy of DWA2114R in killing the cells was 2.6 times greater than that of CDDP in the 3-h treatment at 0 degrees C.

Carboplatin↗

Determination of the target volume of HeLa cells treated with platinum-195m radiolabeled trans-diaminedichloroplatinum(II): a comparison with cis-diaminedichloroplatinum(II).

HeLa S-3 cells were treated with 195mPt-radiolabeled trans-diaminedichloroplatinum(II) (TDDP) under various conditions, and the relationship between lethal effect and the number of Pt atoms binding to DNA, RNA and proteins was examined. The mean lethal concentrations for the cells treated with TDDP at 37 degrees C for 1, 2 and 3 h were 163.7, 65.8 and 24.9 microM, respectively. By using identically treated cells, the number of Pt atoms combined with DNA, RNA and protein molecules was determined after the cells were fractionated using the method of Schneider. In this way, the D0 values given as the drug concentration were substituted for the number of Pt atoms combined with each fraction, then the target volumes, expressed as the reciprocals of the D0 values, were calculated for each fraction. The results suggested that DNA and high molecular weight RNAs (except t-RNA), under some limited condition, could be the target molecules for cell killing by TDDP. The target volumes for DNA were 1.31 x 10(3), 3.01 x 10(3) and 6.26 x 10(3) nucleotides for 1, 2 and 3 h treated cells, respectively. Cell killing effects of TDDP were lower than CDDP by a factor of 39.5, 19.0 and 16.5 for 1, 2 and 3 h treatments at 37 degrees C, respectively, when viewed from the stand point of the target volume, while those from the mean lethal dose (D0) were 17.6, 9.8 and 6.7, respectively.

Cell Survival↗

The number of platinum atoms binding to DNA, RNA and protein molecules of HeLa cells treated with cisplatin at its mean lethal concentration.

HeLa S-3 cells were treated with 195mPt-radiolabeled cis-diamminedichloroplatinum(II) (CDDP) under various conditions, and the relationship between lethal effect and the number of Pt atoms binding to DNA, RNA and proteins was examined. The mean lethal concentrations for the cells treated with CDDP at 37 degrees C for 1, 2 and 3 h were 2.8, 2.0 and 1.1 microgram/ml, respectively. By using identically treated cells, the number of Pt atoms combined with DNA, RNA and protein molecules were determined after fractionation of the cells using the method of Schneider. In this way, the D0 values given as the drug concentration were substituted for the number of Pt atoms combined with each fraction, then the target volumes expressed as the reciprocals of D0 values were calculated for each fraction. The results provide strong support for the idea that DNA is the primary target for cell killing by CDDP, and the target volumes were 5.17 x 10(4), 5.71 x 10(4) and 1.03 x 10(5) nucleotides for 1, 2 and 3 h treated cells, respectively.

Cell Survival↗

Biomedical irradiation system for boron neutron capture therapy at the Kyoto University Reactor.

Physics studies related to radiation source, spectroscopy, beam quality, dosimetry, and biomedical applications using the Kyoto University Reactor Heavy Water Facility are described. Also, described are a Nickel Mirror Neutron Guide Tube and a Super Mirror Neutron Guide Tube that are used both for the measurement of boron concentration in phantom and living tissue and for precise measurements of neutron flux in phantom in the presence of both light and heavy water. Discussed are: (1) spectrum measurements using the time of flight technique, (2) the elimination of gamma rays and fast neutrons from a thermal neutron irradiation field, (3) neutron collimation without producing secondary gamma rays, (4) precise neutron flux measurements, dose estimation, and the measurement of boron concentration in tumor and its periphery using guide tubes, (5) the dose estimation of boron-10 for the first melanoma patient, and (6) special-purpose biological irradiation equipment. Other related subjects are also described.

Biophysical Phenomena↗

Estimation of RBEs of thermal neutrons and reactor beam in the thermal neutron field for biomedical purposes.

The radiation field and reactor beam were prepared to measure the RBE of thermal neutrons and reactor beam in Kyoto University Reactor (KUR). The RBE of reactor beam with low contamination of gamma ray (1.8 x 10(11) n cm-2R-1) and high Cd ratio (5000) on HeLa cells was 1.26 at the surviving fraction of 0.90, and the estimated RBE of thermal neutrons was 5.50 at the same surviving fraction.

Cadmium↗

Nuclear magnetic resonance relaxation times for tissues of mice given radioprotective compounds.

The pharmacological actions of chemical radioprotective substances (superoxide dismutase, cysteamine, beta-aminoethylisothiouronium Br-HBr, and propylene glycol) on mouse tissues were studied by measurement of proton NMR relaxation times. Changes in 1/T1 and 1/T2 values were observed but could not be correlated in any simple manner with the radioprotective actions of the administered compounds. Small but statistically significance correlations between water content and 1/T1 or 1/T2 value were observed.

Animals↗

Comparison of age-associated changes of c-myc gene methylation in liver between man and mouse.

Age-associated changes in DNA methylation of the c-myc gene in liver were compared between humans and mice which have large differences in aging rate. Although the overall methylation profiles of the gene and their age-related changes were found to be similar, the rate of change was much slower in humans than in mice. It suggests that the age-associated alteration of c-myc gene methylation is closely related to biological aging rather than to chronological aging.

Aging↗

Epidemiological studies on disturbances of human fetal development in areas with various doses of natural background radiation. I. Relationship between incidences of Down's syndrome or visible malformation and gonad dose equivalent rate of natural background radiation.

The relationship between environmental radiation (mSv X a-1) to the gonads and incidences of Down's syndrome and visible malformation was analyzed using Kendall's rank correlation method. The subjects, studied during a 3-yr period (1979-1981), were inhabitants of 46 prefectures in Japan that had various dose rates (mu R/h) of natural background ionizing radiation. Results showed that the natural background very low-dose radiation rate was not a predominant factor responsible for inducing Down's syndrome or other visible malformations.

Background Radiation↗

Epidemiological studies on disturbances of human fetal development in areas with various doses of natural background radiation. II. Relationship between incidences of hydatidiform mole, malignant hydatidiform mole, and chorionepithelioma and gonad dose equivalent rate of natural background radiation.

The relationships between gonad dose equivalent rates and incidences of chorionic disease (i.e., hydatidiform mole, malignant hydatidiform mole, and chorionepithelioma) were analyzed with Kendall's rank correlation and regression methods. Data used were from 11 prefectures of Japan with various dose rates of natural background ionizing radiation between the years 1974 to 1976. The results suggested an association of the incidence of chorionic disease with the radiation dose rate in the very low dose-rate range.

Adult↗