Source:http://linkedlifedata.com/resource/pubmed/id/10557052
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
11
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| pubmed:dateCreated |
1999-12-7
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| pubmed:abstractText |
The effect of expression of an O6-benzylguanine (O6-beG)-resistant mutant (hATPA/GA) of human O6-alkylguanine-DNA alkyltransferase (ATase) on the in vivo toxicity and clastogenicity of the anti-tumour agent N,N'-bis(2-chloroethyl)-N-nitrosourea (BCNU) to murine bone marrow has been investigated. When compared with control animals, the bipotent granulocyte-macrophage colony-forming (GM-CFC) progenitor population of the hATPA/GA transduced mice were somewhat more resistant to BCNU (1.4-fold, P = 0.047) and this effect was more significant in the presence of the ATase inactivator O6-beG (3. 5-fold, P = 0.001). The polychromatic erythrocytes were also significantly protected against BCNU-induced clastogenicity both in the presence (P < 0.001) and absence of O6-beG (P < 0.05). The primitive, multipotent spleen colony-forming cells (CFU-S) in these animals also showed moderate (1.6-fold, P = 0.034) protection in the absence of O6-beG but in the presence of the inactivator they remained as sensitive to BCNU toxicity as those in the control animals (P = 0.133). This result contrasts with previous findings demonstrating significant hATPA/GA-mediated, O6-beG-resistant protection against the toxicity and clastogenicity of a number of O6-alkylating agents, including temozolomide, fotemustine and chlorozotocin. The possibility that our strategy for protective gene therapy may be highly agent and cell-type specific is unexpected and has possible implications for clinical trials of this approach using BCNU or related agents.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antineoplastic Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Carmustine,
http://linkedlifedata.com/resource/pubmed/chemical/Guanine,
http://linkedlifedata.com/resource/pubmed/chemical/Mutagens,
http://linkedlifedata.com/resource/pubmed/chemical/Nucleotidyltransferases,
http://linkedlifedata.com/resource/pubmed/chemical/O(6)-benzylguanine,
http://linkedlifedata.com/resource/pubmed/chemical/glutamine-synthetase...
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| pubmed:status |
MEDLINE
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| pubmed:month |
Nov
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| pubmed:issn |
0887-6924
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| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:volume |
13
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
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| pubmed:pagination |
1776-83
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| pubmed:dateRevised |
2006-11-15
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| pubmed:meshHeading |
pubmed-meshheading:10557052-Animals,
pubmed-meshheading:10557052-Antineoplastic Agents,
pubmed-meshheading:10557052-Carmustine,
pubmed-meshheading:10557052-Cells, Cultured,
pubmed-meshheading:10557052-Colony-Forming Units Assay,
pubmed-meshheading:10557052-Drug Resistance, Neoplasm,
pubmed-meshheading:10557052-Erythrocytes,
pubmed-meshheading:10557052-Gene Therapy,
pubmed-meshheading:10557052-Granulocytes,
pubmed-meshheading:10557052-Guanine,
pubmed-meshheading:10557052-Hematopoietic Stem Cells,
pubmed-meshheading:10557052-Humans,
pubmed-meshheading:10557052-Immunohistochemistry,
pubmed-meshheading:10557052-Macrophages,
pubmed-meshheading:10557052-Male,
pubmed-meshheading:10557052-Mice,
pubmed-meshheading:10557052-Micronucleus Tests,
pubmed-meshheading:10557052-Mutagens,
pubmed-meshheading:10557052-Mutation,
pubmed-meshheading:10557052-Nucleotidyltransferases,
pubmed-meshheading:10557052-Spleen,
pubmed-meshheading:10557052-Transduction, Genetic
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| pubmed:year |
1999
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| pubmed:articleTitle |
Protection of committed murine haemopoietic progenitors against BCNU toxicity does not predict protection of primitive, multipotent spleen colony-forming cells - implications for chemoprotective gene therapy.
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| pubmed:affiliation |
CRC Sections of Genome Damage and Repair, Paterson Institute for Cancer Research, Manchester, UK.
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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