Long-term protection of hematopoiesis against the cytotoxic effects of multiple doses of nitrosourea by retrovirus-mediated expression of human O6-alkylguanine-DNA-alkyltransferase.

2.50
Hdl Handle:
http://hdl.handle.net/10541/95845
Title:
Long-term protection of hematopoiesis against the cytotoxic effects of multiple doses of nitrosourea by retrovirus-mediated expression of human O6-alkylguanine-DNA-alkyltransferase.
Authors:
Jelínek, Jaroslav; Fairbairn, Leslie J; Dexter, T Michael; Rafferty, Joseph A; Stocking, C; Ostertag, W; Margison, Geoffrey P
Abstract:
A human O6-alkylguanine-DNA-alkyltransferase (ATase) cDNA-containing retrovirus was used to infect murine long-term primary bone marrow cultures. High levels of ATase expression were obtained, and colony-forming cells of the granulocyte-macrophage lineage from the cultures transduced with the human ATase retrovirus were three times more resistant to the alkylating agent, N-methyl-N-nitrosourea (MNU), than control cultures. Furthermore, expression of the human ATase protected long-term hematopoiesis, measured as the output of progenitor cells to the nonadherent fraction of the culture, against the cytotoxic effects of repeated exposures to MNU. These results clearly show that a human ATase cDNA-containing retrovirus can be used to infect long-term primary bone marrow cultures and that this attenuates their sensitivity to nitrosoureas.
Affiliation:
CRC Department of Experimental Haematology, Paterson Institute for Cancer Research, Christie Hospital NHS Trust, Manchester, UK.
Citation:
Long-term protection of hematopoiesis against the cytotoxic effects of multiple doses of nitrosourea by retrovirus-mediated expression of human O6-alkylguanine-DNA-alkyltransferase. 1996, 87 (5):1957-61 Blood
Journal:
Blood
Issue Date:
1-Mar-1996
URI:
http://hdl.handle.net/10541/95845
PubMed ID:
8634444
Type:
Article
Language:
en
ISSN:
0006-4971
Appears in Collections:
All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorJelínek, Jaroslaven
dc.contributor.authorFairbairn, Leslie Jen
dc.contributor.authorDexter, T Michaelen
dc.contributor.authorRafferty, Joseph Aen
dc.contributor.authorStocking, Cen
dc.contributor.authorOstertag, Wen
dc.contributor.authorMargison, Geoffrey Pen
dc.date.accessioned2010-04-07T10:39:53Z-
dc.date.available2010-04-07T10:39:53Z-
dc.date.issued1996-03-01-
dc.identifier.citationLong-term protection of hematopoiesis against the cytotoxic effects of multiple doses of nitrosourea by retrovirus-mediated expression of human O6-alkylguanine-DNA-alkyltransferase. 1996, 87 (5):1957-61 Blooden
dc.identifier.issn0006-4971-
dc.identifier.pmid8634444-
dc.identifier.urihttp://hdl.handle.net/10541/95845-
dc.description.abstractA human O6-alkylguanine-DNA-alkyltransferase (ATase) cDNA-containing retrovirus was used to infect murine long-term primary bone marrow cultures. High levels of ATase expression were obtained, and colony-forming cells of the granulocyte-macrophage lineage from the cultures transduced with the human ATase retrovirus were three times more resistant to the alkylating agent, N-methyl-N-nitrosourea (MNU), than control cultures. Furthermore, expression of the human ATase protected long-term hematopoiesis, measured as the output of progenitor cells to the nonadherent fraction of the culture, against the cytotoxic effects of repeated exposures to MNU. These results clearly show that a human ATase cDNA-containing retrovirus can be used to infect long-term primary bone marrow cultures and that this attenuates their sensitivity to nitrosoureas.en
dc.language.isoenen
dc.subjectHaematopoiesisen
dc.subjectHaematopoietic Stem Cellsen
dc.subjectCultured Tumour Cellsen
dc.subject.meshAnimals-
dc.subject.meshAntineoplastic Agents, Alkylating-
dc.subject.meshBone Marrow Cells-
dc.subject.meshCells, Cultured-
dc.subject.meshDNA Damage-
dc.subject.meshDNA Repair-
dc.subject.meshDNA, Complementary-
dc.subject.meshGenetic Vectors-
dc.subject.meshHematopoiesis-
dc.subject.meshHematopoietic Stem Cells-
dc.subject.meshHumans-
dc.subject.meshMethylnitrosourea-
dc.subject.meshMethyltransferases-
dc.subject.meshMice-
dc.subject.meshMice, Inbred C57BL-
dc.subject.meshMice, Inbred DBA-
dc.subject.meshO(6)-Methylguanine-DNA Methyltransferase-
dc.subject.meshRecombinant Fusion Proteins-
dc.subject.meshRetroviridae-
dc.subject.meshTransfection-
dc.subject.meshTumor Cells, Cultured-
dc.titleLong-term protection of hematopoiesis against the cytotoxic effects of multiple doses of nitrosourea by retrovirus-mediated expression of human O6-alkylguanine-DNA-alkyltransferase.en
dc.typeArticleen
dc.contributor.departmentCRC Department of Experimental Haematology, Paterson Institute for Cancer Research, Christie Hospital NHS Trust, Manchester, UK.en
dc.identifier.journalBlooden
All Items in Christie are protected by copyright, with all rights reserved, unless otherwise indicated.