Accumulation of degradation products of doxorubicin and pirarubicin formed in cell culture medium within sensitive and resistant cells.
Quantitative study of doxorubicin (Adriamycin), pirarubicin (4'-o-tetrahypyranyladriamycin) and daunorubicin in the nucleus of living cells was performed using microspectrofluorometry. As for the cytotoxic assays, drug-sensitive and drug-resistant K562 cells were incubated for 3 days with concentrations of drug ranging from 4 nM to 1 mM. When drug-sensitive cells were incubated with pirarubicin, the spectrum recorded from inside the nucleus was characteristic of anthracycline intercalated between the base pairs in the nucleus. However, when drug-sensitive cells were incubated with doxorubicin and drug-resistant cells with pirarubicin or doxorubicin, a new fluorescent spectrum was obtained which was due to 7,8-dehydro-9,10-desacetyldoxorubicinone, a pirarubicin and doxorubicin degradation product that is formed in the medium. This compound which is highly lipophilic is taken up rapidly into both sensitive and resistant cells.
Fiallo
M
M
Laboratoire de Physique et Chimie Biomoléculaire, (URA CNRS 198) Université Pierre et Marie Curie, Paris, France.
Laigle
A
A
Borrel
M N
MN
Garnier-Suillerot
A
A
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000818:Animals; D002021:Buffers; D002460:Cell Line / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D003470:Culture Media / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D003630:Daunorubicin / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism*; D004351:Drug Resistance; D008562:Membrane Glycoproteins / Q000378:metabolism; D013050:Spectrometry, Fluorescence; D013997:Time Factors
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D002021:Buffers; D003470:Culture Media; D008562:Membrane Glycoproteins; C079835:7,8-dehydro-9,10-desacetyldoxorubicinone; D004317:Doxorubicin; D004247:DNA; C027260:pirarubicin; D003630:Daunorubicin