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Similarity of apoptosis induction by 2-chlorodeoxyadenosine and cisplatin in human mononuclear blood cells.

The purine analogue 2-chlorodeoxyadenosine (CdA) is unique compared with traditional antimetabolite drugs, as it has shown equal activity in dividing and resting lymphocytes. Poly(ADP-ribose)polymerase (PARP) activation and consecutive NAD+ consumption have been associated with the induction of apop...

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Autores principales: Borner, M. M., Joncourt, F., Hotz, M. A.
Formato: Texto
Lenguaje:English
Publicado: Nature Publishing Group 1997
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2228169/
https://www.ncbi.nlm.nih.gov/pubmed/9400941
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author Borner, M. M.
Joncourt, F.
Hotz, M. A.
author_facet Borner, M. M.
Joncourt, F.
Hotz, M. A.
author_sort Borner, M. M.
collection PubMed
description The purine analogue 2-chlorodeoxyadenosine (CdA) is unique compared with traditional antimetabolite drugs, as it has shown equal activity in dividing and resting lymphocytes. Poly(ADP-ribose)polymerase (PARP) activation and consecutive NAD+ consumption have been associated with the induction of apoptosis in resting cells. The potential of CdA to induce the p53-dependent DNA damage response was assessed in resting and phytohaemagglutinine (PHA)-activated peripheral blood mononuclear cells (PBMCs) and compared with cisplatin (DDP), a cell cycle-dependent and DNA-damaging agent that is mainly used in the treatment of solid tumours. Both drugs induced transactivation of the p53 target genes waf1 and mdm2, NAD+ consumption and apoptotic death. The expression pattern of p53 and waf1 suggests a partly p53-independent induction of waf1. The expression of c-myc and PARP, which both have a dual role in proliferation and apoptosis, was selectively induced by CdA. Cell cycle stimulation increased the cytotoxic activity of both drugs. These data show that DDP is also a potent inducer of apoptosis in resting and proliferating peripheral blood mononuclear cells. Activation of the p53-dependent DNA damage response seems to be an important component of the toxic effect of CdA. IMAGES:
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spelling pubmed-22281692009-09-10 Similarity of apoptosis induction by 2-chlorodeoxyadenosine and cisplatin in human mononuclear blood cells. Borner, M. M. Joncourt, F. Hotz, M. A. Br J Cancer Research Article The purine analogue 2-chlorodeoxyadenosine (CdA) is unique compared with traditional antimetabolite drugs, as it has shown equal activity in dividing and resting lymphocytes. Poly(ADP-ribose)polymerase (PARP) activation and consecutive NAD+ consumption have been associated with the induction of apoptosis in resting cells. The potential of CdA to induce the p53-dependent DNA damage response was assessed in resting and phytohaemagglutinine (PHA)-activated peripheral blood mononuclear cells (PBMCs) and compared with cisplatin (DDP), a cell cycle-dependent and DNA-damaging agent that is mainly used in the treatment of solid tumours. Both drugs induced transactivation of the p53 target genes waf1 and mdm2, NAD+ consumption and apoptotic death. The expression pattern of p53 and waf1 suggests a partly p53-independent induction of waf1. The expression of c-myc and PARP, which both have a dual role in proliferation and apoptosis, was selectively induced by CdA. Cell cycle stimulation increased the cytotoxic activity of both drugs. These data show that DDP is also a potent inducer of apoptosis in resting and proliferating peripheral blood mononuclear cells. Activation of the p53-dependent DNA damage response seems to be an important component of the toxic effect of CdA. IMAGES: Nature Publishing Group 1997 /pmc/articles/PMC2228169/ /pubmed/9400941 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
Borner, M. M.
Joncourt, F.
Hotz, M. A.
Similarity of apoptosis induction by 2-chlorodeoxyadenosine and cisplatin in human mononuclear blood cells.
title Similarity of apoptosis induction by 2-chlorodeoxyadenosine and cisplatin in human mononuclear blood cells.
title_full Similarity of apoptosis induction by 2-chlorodeoxyadenosine and cisplatin in human mononuclear blood cells.
title_fullStr Similarity of apoptosis induction by 2-chlorodeoxyadenosine and cisplatin in human mononuclear blood cells.
title_full_unstemmed Similarity of apoptosis induction by 2-chlorodeoxyadenosine and cisplatin in human mononuclear blood cells.
title_short Similarity of apoptosis induction by 2-chlorodeoxyadenosine and cisplatin in human mononuclear blood cells.
title_sort similarity of apoptosis induction by 2-chlorodeoxyadenosine and cisplatin in human mononuclear blood cells.
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2228169/
https://www.ncbi.nlm.nih.gov/pubmed/9400941
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