ArticleProceedings of the National Academy of Sciences of the United States of America1996
Increasing DNA repair methyltransferase levels via bone marrow stem cell transduction rescues mice from the toxic effects of 1,3-bis(2-chloroethyl)-1-nitrosourea, a chemotherapeutic alkylating agent.
Article in Proceedings of the National Academy of Sciences of the United States of America, 1996. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
24 citing papers in PubMed, 115 citations in OpenAlex.
- Trial
- Engineered packaging cell line for the enhanced production of baboon-enveloped retroviral vectors.Molecular therapy. Nucleic acids · 2024Article
- The Versatile Attributes of MGMT: Its Repair Mechanism, Crosstalk with Other DNA Repair Pathways, and Its Role in Cancer.Cancers · 2024Review
- Protective role of Codiaeum variegatum against genotoxicity induced by carmustine in somatic and germ cells of male mice.Molecular biology reports · 2022Article
- Epidermal growth factor receptor-dependent DNA repair promotes murine and human hematopoietic regeneration.Blood · 2020Article
- SMARCAD1-mediated recruitment of the DNA mismatch repair protein MutLα to MutSα on damaged chromatin induces apoptosis in human cells.The Journal of biological chemistry · 2020Article
- Programming of Cell Resistance to Genotoxic and Oxidative Stress.Biomedicines · 2018Review
- Alkylation and Carbamylation Effects of Lomustine and Its Major Metabolites and MGMT Expression in Canine Cells.Veterinary sciences · 2015Article
- Synthesis and cytotoxicity evaluation of naphthalimide derived N-mustards.Molecules (Basel, Switzerland) · 2014Article
- Knockdown of HPRT for selection of genetically modified human hematopoietic progenitor cells.PloS one · 2013Article
- Balancing repair and tolerance of DNA damage caused by alkylating agents.Nature reviews. Cancer · 2012Review
- A rapid survival assay to measure drug-induced cytotoxicity and cell cycle effects.DNA repair · 2012Article
- Enhancement of radiosensitivity in human glioblastoma cells by the DNA N-mustard alkylating agent BO-1051 through augmented and sustained DNA damage response.Radiation oncology (London, England) · 2011Article
- Targeting O⁶-methylguanine-DNA methyltransferase with specific inhibitors as a strategy in cancer therapy.Cellular and molecular life sciences : CMLS · 2010Review
- Co-expression of MGMT(P140K) and alpha-L-iduronidase in primary hepatocytes from mucopolysaccharidosis type I mice enables efficient selection with metabolic correction.The journal of gene medicine · 2008Article
- Gene therapy approaches for stem cell protection.Gene therapy · 2008Review
- Article
- Vector design for expression of O6-methylguanine-DNA methyltransferase in hematopoietic cells.DNA repair · 2007Review
- Hematoprotection and enrichment of transduced cells in vivo after gene transfer of MGMT(P140K) into hematopoietic stem cells.Cancer gene therapy · 2002Article
- Review
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
The chloroethylnitrosourea (CNU) alkylating agents are commonly used for cancer chemotherapy, but their usefulness is limited by severe bone marrow toxicity that causes the cumulative depletion of all hematopoietic lineages (pancytopenia). Bone marrow CNU sensitivity is probably due to the inefficient repair of CNU-induced DNA damage; relative to other tissues, bone marrow cells express extremely low levels of the O6-methylguanine DNA methyltransferase (MGMT) protein that repairs cytotoxic O6-chloroethylguanine DNA lesions. Using a simplified recombinant retroviral vector expressing the human MGMT gene under control of the phosphoglycerate kinase promoter (PGK-MGMT) we increased the capacity of murine bone marrow-derived cells to repair CNU-induced DNA damage. Stable reconstitution of mouse bone marrow with genetically modified, MGMT-expressing hematopoietic stem cells conferred considerable resistance to the cytotoxic effects of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU), a CNU commonly used for chemotherapy. Bone marrow harvested from mice transplanted with PGK-MGMT-transduced cells showed extensive in vitro BCNU resistance. Moreover, MGMT expression in mouse bone marrow conferred in vivo resistance to BCNU-induced pancytopenia and significantly reduced BCNU-induced mortality due to bone marrow hypoplasia. These data demonstrate that increased DNA alkylation repair in primitive hematopoietic stem cells confers multilineage protection from the myelosuppressive effects of BCNU and suggest a possible approach to protecting cancer patients from CNU chemotherapy-related toxicity.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.