Abstract |
MDR gene expression in murine leukemia L 1210 cells was investigated during treatment in vivo with 0.5 mg doxorubicin/kg body weight (BW). Drug resistance (measured by an in vitro short-term test and immunohistochemistry) increased with the number of treatments and the maximum resistance reached after 8 treatments was similar with that of an established multidrug- resistant cell line (20 treatments, 2 mg/kg BW). Southern-blot and DNA dot-blot analyses show that development of MDR is associated with MDR-gene amplification and correlates with the degree of drug resistance and P-glycoprotein-expression. After cessation of doxorubicin treatment, resistance decreased continuously and disappeared after 20 passages. This decrease in resistance is accompanied by a loss of MDR gene amplification and P-glycoprotein expression. Furthermore, P-glycoprotein expression was analyzed in the first hours after treatment with doxorubicin in vivo (0.5 mg/kg BW). Expression was markedly increased and peaked at about 24 hours after treatment. In contrast, only slightly increased resistance and no MDR gene amplification could be detected.
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Authors | M Volm, J Mattern, E W Pommerenke |
Journal | Anticancer research
(Anticancer Res)
1991 Mar-Apr
Vol. 11
Issue 2
Pg. 579-85
ISSN: 0250-7005 [Print] Greece |
PMID | 1676579
(Publication Type: Journal Article)
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Chemical References |
- ATP Binding Cassette Transporter, Subfamily B, Member 1
- Antibodies, Monoclonal
- DNA, Neoplasm
- Membrane Glycoproteins
- Doxorubicin
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Topics |
- ATP Binding Cassette Transporter, Subfamily B, Member 1
- Animals
- Antibodies, Monoclonal
- Blotting, Southern
- Cell Survival
(drug effects)
- DNA, Neoplasm
(genetics, isolation & purification)
- Dose-Response Relationship, Drug
- Doxorubicin
(pharmacology)
- Drug Resistance
(genetics)
- Female
- Gene Amplification
- Immunohistochemistry
- Kinetics
- Leukemia L1210
(genetics)
- Membrane Glycoproteins
(analysis, genetics)
- Mice
- Mice, Inbred Strains
- Time Factors
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