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.     

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.     

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.     

Subject Index

Summary

Double-strand breaks and regions with unpaired bases (S1-nuclease sensitive sites) are formed in the DNA of γ-irradiated λ-phages. The frequency of both events was determined in the various fragments produced after digestion with a restriction enzyme (Eco RI). The results show that both types of radiation damage are randomly distributed in the DNA molecule. There is no hint that the S1 sites are formed in preferred regions of the λ-genome.     

Binding Characteristics of (–)-(R)-2-Aminomethylpyrrolidine(1,1-cyclobutanedi-carboxylato)-2-platinum(II) to DNA, RNA and Protein Molecules in HeLa Cells and Its Lethal Effect: Comparison with cis- and trans-Diammmedichloroplatinums(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°C for 1, 2 and 3 h were 137.3, 75.10 and 51.17 μM , 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 DWA-2114R. The target volumes for DNA were 3.36 × 10⁴, 4.00 × 10⁴ and 4.10 × 10⁴ nucleotides for 1-, 2-and 3-h treated cells, respectively. The cell-killing effects of DWA2114R were lower than those of cis -dianuninedichloroplatinum(II) (CDDP) by factors of 1.54, 1.42 and 2.51 for 1-, 2- and 3-h treatments at 37°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°C.     

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°C for 1, 2 and 3 h were 2.8, 2.0 and 1.1 μg/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 Do 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 Do 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 × 10⁴, 5.71 × 10⁴ and 1.03 × 10⁴ nucleotides for 1, 2 and 3 h treated cells, respectively.