The effects of dose, route of administration, drug scheduling and MDR-1 gene transfer on the genotoxicity of etoposide in bone marrow.
Authors
Turner, S DRafferty, Joseph A
Fairbairn, Leslie J
Ashby, J
Tinwell, H
Eckert, H G
Baum, C
Lashford, Linda S
Affiliation
Department of Experimental Haematology, Paterson Institute for Cancer Research, Manchester, UK.Issue Date
2000-10
Metadata
Show full item recordAbstract
We have used the bone marrow micronucleus assay (BMMN) as a measure of clastogenicity, in response to etoposide exposure in murine bone marrow. Oral delivery of etoposide resulted in a reduced number of micronucleated polychromatic erythrocytes (MPE) relative to the same dose delivered intraperitoneally (P < 0.001). Daily fractionation of the oral schedule of etoposide led to a more than six-fold increase in cumulative MPE frequency over that observed with the same total, unfractionated dose, with the potency of the response increasing with serial exposure (r = 0.79). Retrovirally-mediated expression of MDR1 in murine bone marrow resulted in partial protection against the clastogenic activity of etoposide relative to mock transduced control mice. The model system developed has indicated a variety of factors able to influence the genotoxicity of etoposide. It should now be possible to further exploit this model in order to define other factors governing haemopoietic sensitivity to etoposide.Citation
The effects of dose, route of administration, drug scheduling and MDR-1 gene transfer on the genotoxicity of etoposide in bone marrow. 2000, 14 (10):1796-802 LeukemiaJournal
LeukemiaPubMed ID
11021755Type
ArticleLanguage
enISSN
0887-6924Related articles
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