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 × 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.