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Pharmacodynamics of cisplatin in human head and neck cancer: correlation between platinum content, DNA adduct levels and drug sensitivity in vitro and in vivo
Total platinum contents and cisplatin–DNA adduct levels were determined in vivo in xenografted tumour tissues in mice and in vitro in cultured tumour cells of head and neck squamous cell carcinoma (HNSCC), and correlated with sensitivity to cisplatin. In vivo, a panel of five HNSCC tumour lines grow...
Autores principales: | , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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Nature Publishing Group
1999
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2362173/ https://www.ncbi.nlm.nih.gov/pubmed/10408697 http://dx.doi.org/10.1038/sj.bjc.6690015 |
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author | Welters, M J P Fichtinger-Schepman, A M J Baan, R A Jacobs-Bergmans, A J Kegel, A van der Vijgh, W J F Braakhuis, B J M |
author_facet | Welters, M J P Fichtinger-Schepman, A M J Baan, R A Jacobs-Bergmans, A J Kegel, A van der Vijgh, W J F Braakhuis, B J M |
author_sort | Welters, M J P |
collection | PubMed |
description | Total platinum contents and cisplatin–DNA adduct levels were determined in vivo in xenografted tumour tissues in mice and in vitro in cultured tumour cells of head and neck squamous cell carcinoma (HNSCC), and correlated with sensitivity to cisplatin. In vivo, a panel of five HNSCC tumour lines growing as xenografts in nude mice was used. In vitro, the panel consisted of five HNSCC cell lines, of which four had an in vivo equivalent. Sensitivity to cisplatin varied three- to sevenfold among cell lines and tumours respectively. However, the ranking of the sensitivities of the tumour lines (in vivo), also after reinjection of the cultured tumour cells, did not coincide with that of the corresponding cell lines, which showed that cell culture systems are not representative for the in vivo situation. Both in vitro and in vivo, however, significant correlations were found between total platinum levels, measured by atomic absorption spectrophotometry (AAS), and tumour response to cisplatin therapy at all time points tested. The levels of the two major cisplatin–DNA adduct types were determined by a recently developed and improved(32)P post-labelling assay at various time points after cisplatin treatment. Evidence is presented that the platinum–AG adduct, in which platinum is bound to guanine and an adjacent adenine, may be the cytotoxic lesion because a significant correlation was found between the platinum–AG levels and the sensitivities in our panel of HNSCC, in vitro as well as in vivo. This correlation with the platinum–AG levels was established at 1 h (in vitro) and 3 h (in vivo) after the start of the cisplatin treatment, which emphasizes the importance of early sampling. © 1999 Cancer Research Campaign |
format | Text |
id | pubmed-2362173 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 1999 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-23621732009-09-10 Pharmacodynamics of cisplatin in human head and neck cancer: correlation between platinum content, DNA adduct levels and drug sensitivity in vitro and in vivo Welters, M J P Fichtinger-Schepman, A M J Baan, R A Jacobs-Bergmans, A J Kegel, A van der Vijgh, W J F Braakhuis, B J M Br J Cancer Regular Article Total platinum contents and cisplatin–DNA adduct levels were determined in vivo in xenografted tumour tissues in mice and in vitro in cultured tumour cells of head and neck squamous cell carcinoma (HNSCC), and correlated with sensitivity to cisplatin. In vivo, a panel of five HNSCC tumour lines growing as xenografts in nude mice was used. In vitro, the panel consisted of five HNSCC cell lines, of which four had an in vivo equivalent. Sensitivity to cisplatin varied three- to sevenfold among cell lines and tumours respectively. However, the ranking of the sensitivities of the tumour lines (in vivo), also after reinjection of the cultured tumour cells, did not coincide with that of the corresponding cell lines, which showed that cell culture systems are not representative for the in vivo situation. Both in vitro and in vivo, however, significant correlations were found between total platinum levels, measured by atomic absorption spectrophotometry (AAS), and tumour response to cisplatin therapy at all time points tested. The levels of the two major cisplatin–DNA adduct types were determined by a recently developed and improved(32)P post-labelling assay at various time points after cisplatin treatment. Evidence is presented that the platinum–AG adduct, in which platinum is bound to guanine and an adjacent adenine, may be the cytotoxic lesion because a significant correlation was found between the platinum–AG levels and the sensitivities in our panel of HNSCC, in vitro as well as in vivo. This correlation with the platinum–AG levels was established at 1 h (in vitro) and 3 h (in vivo) after the start of the cisplatin treatment, which emphasizes the importance of early sampling. © 1999 Cancer Research Campaign Nature Publishing Group 1999-01 1999-09-24 /pmc/articles/PMC2362173/ /pubmed/10408697 http://dx.doi.org/10.1038/sj.bjc.6690015 Text en Copyright © 1999 Cancer Research Campaign 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 | Regular Article Welters, M J P Fichtinger-Schepman, A M J Baan, R A Jacobs-Bergmans, A J Kegel, A van der Vijgh, W J F Braakhuis, B J M Pharmacodynamics of cisplatin in human head and neck cancer: correlation between platinum content, DNA adduct levels and drug sensitivity in vitro and in vivo |
title | Pharmacodynamics of cisplatin in human head and neck cancer: correlation between platinum content, DNA adduct levels and drug sensitivity in vitro and in vivo |
title_full | Pharmacodynamics of cisplatin in human head and neck cancer: correlation between platinum content, DNA adduct levels and drug sensitivity in vitro and in vivo |
title_fullStr | Pharmacodynamics of cisplatin in human head and neck cancer: correlation between platinum content, DNA adduct levels and drug sensitivity in vitro and in vivo |
title_full_unstemmed | Pharmacodynamics of cisplatin in human head and neck cancer: correlation between platinum content, DNA adduct levels and drug sensitivity in vitro and in vivo |
title_short | Pharmacodynamics of cisplatin in human head and neck cancer: correlation between platinum content, DNA adduct levels and drug sensitivity in vitro and in vivo |
title_sort | pharmacodynamics of cisplatin in human head and neck cancer: correlation between platinum content, dna adduct levels and drug sensitivity in vitro and in vivo |
topic | Regular Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2362173/ https://www.ncbi.nlm.nih.gov/pubmed/10408697 http://dx.doi.org/10.1038/sj.bjc.6690015 |
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