Long-term protection of hematopoiesis against the cytotoxic effects of multiple doses of nitrosourea by retrovirus-mediated expression of human O6-alkylguanine-DNA-alkyltransferase
| Autor: | J Jelinek, LJ Fairbairn, TM Dexter, JA Rafferty, C Stocking, W Ostertag, GP Margison |
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| Rok vydání: | 1996 |
| Předmět: | |
| Zdroj: | Blood. 87:1957-1961 |
| ISSN: | 1528-0020 0006-4971 |
| DOI: | 10.1182/blood.v87.5.1957.bloodjournal8751957 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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