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CNS progenitor cells and oligodendrocytes are targets of chemotherapeutic agents in vitro and in vivo

BACKGROUND: Chemotherapy in cancer patients can be associated with serious short- and long-term adverse neurological effects, such as leukoencephalopathy and cognitive impairment, even when therapy is delivered systemically. The underlying cellular basis for these adverse effects is poorly understoo...

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Detalles Bibliográficos
Autores principales: Dietrich, Joerg, Han, Ruolan, Yang, Yin, Mayer-Pröschel, Margot, Noble, Mark
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2006
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2000477/
https://www.ncbi.nlm.nih.gov/pubmed/17125495
http://dx.doi.org/10.1186/jbiol50
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author Dietrich, Joerg
Han, Ruolan
Yang, Yin
Mayer-Pröschel, Margot
Noble, Mark
author_facet Dietrich, Joerg
Han, Ruolan
Yang, Yin
Mayer-Pröschel, Margot
Noble, Mark
author_sort Dietrich, Joerg
collection PubMed
description BACKGROUND: Chemotherapy in cancer patients can be associated with serious short- and long-term adverse neurological effects, such as leukoencephalopathy and cognitive impairment, even when therapy is delivered systemically. The underlying cellular basis for these adverse effects is poorly understood. RESULTS: We found that three mainstream chemotherapeutic agents – carmustine (BCNU), cisplatin, and cytosine arabinoside (cytarabine), representing two DNA cross-linking agents and an antimetabolite, respectively – applied at clinically relevant exposure levels to cultured cells are more toxic for the progenitor cells of the CNS and for nondividing oligodendrocytes than they are for multiple cancer cell lines. Enhancement of cell death and suppression of cell division were seen in vitro and in vivo. When administered systemically in mice, these chemotherapeutic agents were associated with increased cell death and decreased cell division in the subventricular zone, in the dentate gyrus of the hippocampus and in the corpus callosum of the CNS. In some cases, cell division was reduced, and cell death increased, for weeks after drug administration ended. CONCLUSION: Identifying neural populations at risk during any cancer treatment is of great importance in developing means of reducing neurotoxicity and preserving quality of life in long-term survivors. Thus, as well as providing possible explanations for the adverse neurological effects of systemic chemotherapy, the strong correlations between our in vitro and in vivo analyses indicate that the same approaches we used to identify the reported toxicities can also provide rapid in vitro screens for analyzing new therapies and discovering means of achieving selective protection or targeted killing.
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spelling pubmed-20004772007-10-05 CNS progenitor cells and oligodendrocytes are targets of chemotherapeutic agents in vitro and in vivo Dietrich, Joerg Han, Ruolan Yang, Yin Mayer-Pröschel, Margot Noble, Mark J Biol Research Article BACKGROUND: Chemotherapy in cancer patients can be associated with serious short- and long-term adverse neurological effects, such as leukoencephalopathy and cognitive impairment, even when therapy is delivered systemically. The underlying cellular basis for these adverse effects is poorly understood. RESULTS: We found that three mainstream chemotherapeutic agents – carmustine (BCNU), cisplatin, and cytosine arabinoside (cytarabine), representing two DNA cross-linking agents and an antimetabolite, respectively – applied at clinically relevant exposure levels to cultured cells are more toxic for the progenitor cells of the CNS and for nondividing oligodendrocytes than they are for multiple cancer cell lines. Enhancement of cell death and suppression of cell division were seen in vitro and in vivo. When administered systemically in mice, these chemotherapeutic agents were associated with increased cell death and decreased cell division in the subventricular zone, in the dentate gyrus of the hippocampus and in the corpus callosum of the CNS. In some cases, cell division was reduced, and cell death increased, for weeks after drug administration ended. CONCLUSION: Identifying neural populations at risk during any cancer treatment is of great importance in developing means of reducing neurotoxicity and preserving quality of life in long-term survivors. Thus, as well as providing possible explanations for the adverse neurological effects of systemic chemotherapy, the strong correlations between our in vitro and in vivo analyses indicate that the same approaches we used to identify the reported toxicities can also provide rapid in vitro screens for analyzing new therapies and discovering means of achieving selective protection or targeted killing. BioMed Central 2006 2006-11-30 /pmc/articles/PMC2000477/ /pubmed/17125495 http://dx.doi.org/10.1186/jbiol50 Text en Copyright © 2006 Dietrich et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Dietrich, Joerg
Han, Ruolan
Yang, Yin
Mayer-Pröschel, Margot
Noble, Mark
CNS progenitor cells and oligodendrocytes are targets of chemotherapeutic agents in vitro and in vivo
title CNS progenitor cells and oligodendrocytes are targets of chemotherapeutic agents in vitro and in vivo
title_full CNS progenitor cells and oligodendrocytes are targets of chemotherapeutic agents in vitro and in vivo
title_fullStr CNS progenitor cells and oligodendrocytes are targets of chemotherapeutic agents in vitro and in vivo
title_full_unstemmed CNS progenitor cells and oligodendrocytes are targets of chemotherapeutic agents in vitro and in vivo
title_short CNS progenitor cells and oligodendrocytes are targets of chemotherapeutic agents in vitro and in vivo
title_sort cns progenitor cells and oligodendrocytes are targets of chemotherapeutic agents in vitro and in vivo
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2000477/
https://www.ncbi.nlm.nih.gov/pubmed/17125495
http://dx.doi.org/10.1186/jbiol50
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