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Relationship between Cell‐killing Efficiency and Number of Platinum Atoms Binding to DNA, RNA, and Protein Molecules in HeLa Cells Treated with cis‐Diamine(glycolato)platinum(II)
HeLa S‐3 cells were treated with (195m)Pt‐radiolabeled cis‐diamine(glycolato)platinum(II) (254‐S) under various conditions, and the relationship between the lethal effect and the numbers of Pt atoms binding to DNA, RNA, and proteins was examined. The mean lethal concentrations for the cells treated...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Blackwell Publishing Ltd
1996
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5921063/ https://www.ncbi.nlm.nih.gov/pubmed/8609067 http://dx.doi.org/10.1111/j.1349-7006.1996.tb03156.x |
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author | Akaboshi, Mitsuhiko Kawai, Kenichi Kinashi, Yuko Masunaga, Shinichiro Ono, Koji |
author_facet | Akaboshi, Mitsuhiko Kawai, Kenichi Kinashi, Yuko Masunaga, Shinichiro Ono, Koji |
author_sort | Akaboshi, Mitsuhiko |
collection | PubMed |
description | HeLa S‐3 cells were treated with (195m)Pt‐radiolabeled cis‐diamine(glycolato)platinum(II) (254‐S) under various conditions, and the relationship between the lethal effect and the numbers of Pt atoms binding to DNA, RNA, and proteins was examined. The mean lethal concentrations for the cells treated with 254‐S at 37°C for 0.5, 1, 2, and 3 h were 67.1, 47.0, 26.8 and 8.1 μM(1), respectively. Using identically treated cells, we determined the numbers of Pt atoms combined with DNA, RNA, and protein molecules after fractionation of the cells. In this way, the D(0) values (D(0), the dose that causes an average of one lethal event per member of the population), expressed as the drug concentration, could he related to the number of Pt atoms combined with each fraction. The efficiency of the Pt atom in killing the cells, expressed as the reciprocal of the D(0) values, was then calculated for each fraction. The results suggested that DNA was the primary target for cell killing by 254‐S. The target volumes for DNA were 3.96, 4.97, and 11.77 × 10(4) nucleotides for 1‐, 2‐, and 3‐h treated cells, respectively. In terms of the target volume, the cell‐killing effects of 254‐S were comparable to those of cis‐diamine‐dichloroplatinum(II) (CDDP), for which the target volumes under identical conditions were determined to be 5.17, 5.71, and 10.3 × 10(4) nucleotides, respectively, while in terms of the mean lethal dose (D(0)), the cell‐killing effects of 254‐S were lower than those of CDDP by a factor of 5.1 (47.0/9.3), 4.0 (26.8/6.7), or 2.5 (8.1/3.2) for 1‐, 2‐, or 3‐h treatment, respectively. |
format | Online Article Text |
id | pubmed-5921063 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 1996 |
publisher | Blackwell Publishing Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-59210632018-05-11 Relationship between Cell‐killing Efficiency and Number of Platinum Atoms Binding to DNA, RNA, and Protein Molecules in HeLa Cells Treated with cis‐Diamine(glycolato)platinum(II) Akaboshi, Mitsuhiko Kawai, Kenichi Kinashi, Yuko Masunaga, Shinichiro Ono, Koji Jpn J Cancer Res Article HeLa S‐3 cells were treated with (195m)Pt‐radiolabeled cis‐diamine(glycolato)platinum(II) (254‐S) under various conditions, and the relationship between the lethal effect and the numbers of Pt atoms binding to DNA, RNA, and proteins was examined. The mean lethal concentrations for the cells treated with 254‐S at 37°C for 0.5, 1, 2, and 3 h were 67.1, 47.0, 26.8 and 8.1 μM(1), respectively. Using identically treated cells, we determined the numbers of Pt atoms combined with DNA, RNA, and protein molecules after fractionation of the cells. In this way, the D(0) values (D(0), the dose that causes an average of one lethal event per member of the population), expressed as the drug concentration, could he related to the number of Pt atoms combined with each fraction. The efficiency of the Pt atom in killing the cells, expressed as the reciprocal of the D(0) values, was then calculated for each fraction. The results suggested that DNA was the primary target for cell killing by 254‐S. The target volumes for DNA were 3.96, 4.97, and 11.77 × 10(4) nucleotides for 1‐, 2‐, and 3‐h treated cells, respectively. In terms of the target volume, the cell‐killing effects of 254‐S were comparable to those of cis‐diamine‐dichloroplatinum(II) (CDDP), for which the target volumes under identical conditions were determined to be 5.17, 5.71, and 10.3 × 10(4) nucleotides, respectively, while in terms of the mean lethal dose (D(0)), the cell‐killing effects of 254‐S were lower than those of CDDP by a factor of 5.1 (47.0/9.3), 4.0 (26.8/6.7), or 2.5 (8.1/3.2) for 1‐, 2‐, or 3‐h treatment, respectively. Blackwell Publishing Ltd 1996-02 /pmc/articles/PMC5921063/ /pubmed/8609067 http://dx.doi.org/10.1111/j.1349-7006.1996.tb03156.x Text en |
spellingShingle | Article Akaboshi, Mitsuhiko Kawai, Kenichi Kinashi, Yuko Masunaga, Shinichiro Ono, Koji Relationship between Cell‐killing Efficiency and Number of Platinum Atoms Binding to DNA, RNA, and Protein Molecules in HeLa Cells Treated with cis‐Diamine(glycolato)platinum(II) |
title | Relationship between Cell‐killing Efficiency and Number of Platinum Atoms Binding to DNA, RNA, and Protein Molecules in HeLa Cells Treated with cis‐Diamine(glycolato)platinum(II) |
title_full | Relationship between Cell‐killing Efficiency and Number of Platinum Atoms Binding to DNA, RNA, and Protein Molecules in HeLa Cells Treated with cis‐Diamine(glycolato)platinum(II) |
title_fullStr | Relationship between Cell‐killing Efficiency and Number of Platinum Atoms Binding to DNA, RNA, and Protein Molecules in HeLa Cells Treated with cis‐Diamine(glycolato)platinum(II) |
title_full_unstemmed | Relationship between Cell‐killing Efficiency and Number of Platinum Atoms Binding to DNA, RNA, and Protein Molecules in HeLa Cells Treated with cis‐Diamine(glycolato)platinum(II) |
title_short | Relationship between Cell‐killing Efficiency and Number of Platinum Atoms Binding to DNA, RNA, and Protein Molecules in HeLa Cells Treated with cis‐Diamine(glycolato)platinum(II) |
title_sort | relationship between cell‐killing efficiency and number of platinum atoms binding to dna, rna, and protein molecules in hela cells treated with cis‐diamine(glycolato)platinum(ii) |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5921063/ https://www.ncbi.nlm.nih.gov/pubmed/8609067 http://dx.doi.org/10.1111/j.1349-7006.1996.tb03156.x |
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