A lack of detectable modification of topoisomerase II activity in a series of human tumor cell lines expressing only low levels of etoposide resistance.
Etoposide (VP-16) resistance is expressed following in vitro exposure of HN-1 and MCF-7 human tumor cells to the drug itself or to fractionated X irradiation. VP-16-selected sublines prove cross-resistant to Adriamycin, amsacrine and actinomycin D, whilst X-ray-pretreated sublines show cross-resistance to only actinomycin D. These differential responses, in the HN-1 series, are not associated with significant differences in amounts of immunoreactive topoisomerase (topo) II, altered topo-II catalytic activity of nuclear extracts or changes in susceptibility of the topo II to VP-16- or amsacrine-induced DNA-protein cross-link formation. Therefore significant modifications in topo II appear not to be implicated in VP-16 resistance in these HN-1 sublines.
Hill
B T
BT
Laboratory of Cellular Chemotherapy, Imperial Cancer Research Fund, London, UK.
Whelan
R D
RD
Hosking
L K
LK
Shellard
S A
SA
Hinds
M D
MD
Mayes
J
J
Zwelling
L A
LA
D000677:Amsacrine / Q000494:pharmacology; D001943:Breast Neoplasms; D002460:Cell Line; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D004249:DNA Damage; D004250:DNA Topoisomerases, Type II / Q000378:metabolism*; D004273:DNA, Neoplasm / Q000378:metabolism; D004351:Drug Resistance; D005047:Etoposide / Q000494:pharmacology*; D005260:Female; D006801:Humans; D015151:Immunoblotting
D004273:DNA, Neoplasm; D000677:Amsacrine; D005047:Etoposide; D004250:DNA Topoisomerases, Type II