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DNA damage and sequence specificity of DNA binding of the new anti-cancer agent 1,4-bis(2'-chloroethyl)-1,4-diazabicyclo-[2.2.1] heptane dimaleate (Dabis maleate)
The DNA damage and the sequence specificity of guanine-N7 alkylation produced by the novel, positively charged, antineoplastic agent 1,4-bis(2'-chloroethyl)-1,4-diazabicyclo-[2.2.1] heptane dimaleate (Dabis maleate) and its uncharged tertiary amine analogue 1,4-bis(2'-chloroethyl)-1,4-diaz...
Autores principales: | , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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Nature Publishing Group
1990
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1971404/ https://www.ncbi.nlm.nih.gov/pubmed/2393411 |
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author | Broggini, M. Hartley, J. A. Mattes, W. B. Ponti, M. Kohn, K. W. D'Incalci, M. |
author_facet | Broggini, M. Hartley, J. A. Mattes, W. B. Ponti, M. Kohn, K. W. D'Incalci, M. |
author_sort | Broggini, M. |
collection | PubMed |
description | The DNA damage and the sequence specificity of guanine-N7 alkylation produced by the novel, positively charged, antineoplastic agent 1,4-bis(2'-chloroethyl)-1,4-diazabicyclo-[2.2.1] heptane dimaleate (Dabis maleate) and its uncharged tertiary amine analogue 1,4-bis(2'-chloroethyl)-1,4-diazacyclohexane (Dabis analogue) were investigated in L1210 cells and isolated DNA. Both compounds are cytotoxic in vitro causing an arrest of L1210 cells in G2/M phase of the cell cycle. In isolated DNA, Dabis maleate alkylates guanine at the N7-position with some differences in specificity compared to other alkylating agents (e.g. nitrogen mustard). Significant differences are also evident between Dabis maleate and Dabis analogue, suggesting that Dabis analogue is not the sole alkylating species of Dabis maleate. Using the alkaline elution technique a moderate number of DNA interstrand cross-links were detected in L1210 cells treated with both compounds, which were completely repaired within 24 h. Dabis maleate and Dabis analogue do not cause DNA single strand breaks or DNA protein cross-links at the doses at which DNA interstrand cross-links were detected. |
format | Text |
id | pubmed-1971404 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 1990 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-19714042009-09-10 DNA damage and sequence specificity of DNA binding of the new anti-cancer agent 1,4-bis(2'-chloroethyl)-1,4-diazabicyclo-[2.2.1] heptane dimaleate (Dabis maleate) Broggini, M. Hartley, J. A. Mattes, W. B. Ponti, M. Kohn, K. W. D'Incalci, M. Br J Cancer Research Article The DNA damage and the sequence specificity of guanine-N7 alkylation produced by the novel, positively charged, antineoplastic agent 1,4-bis(2'-chloroethyl)-1,4-diazabicyclo-[2.2.1] heptane dimaleate (Dabis maleate) and its uncharged tertiary amine analogue 1,4-bis(2'-chloroethyl)-1,4-diazacyclohexane (Dabis analogue) were investigated in L1210 cells and isolated DNA. Both compounds are cytotoxic in vitro causing an arrest of L1210 cells in G2/M phase of the cell cycle. In isolated DNA, Dabis maleate alkylates guanine at the N7-position with some differences in specificity compared to other alkylating agents (e.g. nitrogen mustard). Significant differences are also evident between Dabis maleate and Dabis analogue, suggesting that Dabis analogue is not the sole alkylating species of Dabis maleate. Using the alkaline elution technique a moderate number of DNA interstrand cross-links were detected in L1210 cells treated with both compounds, which were completely repaired within 24 h. Dabis maleate and Dabis analogue do not cause DNA single strand breaks or DNA protein cross-links at the doses at which DNA interstrand cross-links were detected. Nature Publishing Group 1990-02 /pmc/articles/PMC1971404/ /pubmed/2393411 Text en https://creativecommons.org/licenses/by/4.0/This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit https://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Research Article Broggini, M. Hartley, J. A. Mattes, W. B. Ponti, M. Kohn, K. W. D'Incalci, M. DNA damage and sequence specificity of DNA binding of the new anti-cancer agent 1,4-bis(2'-chloroethyl)-1,4-diazabicyclo-[2.2.1] heptane dimaleate (Dabis maleate) |
title | DNA damage and sequence specificity of DNA binding of the new anti-cancer agent 1,4-bis(2'-chloroethyl)-1,4-diazabicyclo-[2.2.1] heptane dimaleate (Dabis maleate) |
title_full | DNA damage and sequence specificity of DNA binding of the new anti-cancer agent 1,4-bis(2'-chloroethyl)-1,4-diazabicyclo-[2.2.1] heptane dimaleate (Dabis maleate) |
title_fullStr | DNA damage and sequence specificity of DNA binding of the new anti-cancer agent 1,4-bis(2'-chloroethyl)-1,4-diazabicyclo-[2.2.1] heptane dimaleate (Dabis maleate) |
title_full_unstemmed | DNA damage and sequence specificity of DNA binding of the new anti-cancer agent 1,4-bis(2'-chloroethyl)-1,4-diazabicyclo-[2.2.1] heptane dimaleate (Dabis maleate) |
title_short | DNA damage and sequence specificity of DNA binding of the new anti-cancer agent 1,4-bis(2'-chloroethyl)-1,4-diazabicyclo-[2.2.1] heptane dimaleate (Dabis maleate) |
title_sort | dna damage and sequence specificity of dna binding of the new anti-cancer agent 1,4-bis(2'-chloroethyl)-1,4-diazabicyclo-[2.2.1] heptane dimaleate (dabis maleate) |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1971404/ https://www.ncbi.nlm.nih.gov/pubmed/2393411 |
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