Long-term protection of hematopoiesis against the cytotoxic effects of multiple doses of nitrosourea by retrovirus-mediated expression of human O6-alkylguanine-DNA-alkyltransferase.
Jelínek, Jaroslav Fairbairn, Leslie J Dexter, T Michael Rafferty, Joseph A Stocking, C Ostertag, W Margison, Geoffrey P
Jelínek, Jaroslav
Fairbairn, Leslie J
Dexter, T Michael
Rafferty, Joseph A
Stocking, C
Ostertag, W
Margison, Geoffrey P
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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.
Description
Date
1996-03-01
Publisher
Collections
Keywords
Haematopoiesis
Haematopoietic Stem Cells
Cultured Tumour Cells
Haematopoietic Stem Cells
Cultured Tumour Cells
Type
Article
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