title: A lack of detectable modification of topoisomerase II activity in a series of human tumor cell lines expressing only low levels of etoposide resistance.
abstract: 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.
authors.affiliation: Laboratory of Cellular Chemotherapy, Imperial Cancer Research Fund, London, UK.
authors.forename: B T
authors.initials: BT
authors.lastname: Hill
authors.forename: R D
authors.initials: RD
authors.lastname: Whelan
authors.forename: L K
authors.initials: LK
authors.lastname: Hosking
authors.forename: S A
authors.initials: SA
authors.lastname: Shellard
authors.forename: M D
authors.initials: MD
authors.lastname: Hinds
authors.forename: J
authors.initials: J
authors.lastname: Mayes
authors.forename: L A
authors.initials: LA
authors.lastname: Zwelling
mesh_terms: 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
chemical_list: D004273:DNA, Neoplasm; D000677:Amsacrine; D005047:Etoposide; D004250:DNA Topoisomerases, Type II