Altered DNA topoisomerase II activity in XXXX cells resistant to topoisomerase II inhibitors.

@entity1 @entity1219 @entity2879 @entity3569 @entity5256
Most DNA intercalators and epipodophyllotoxins inhibit @entity1 topoisomerase II by trapping the enzyme within DNA cleavage complexes that can be detected in cells as protein-associated DNA strand breaks. We have characterized previously a line of @entity3569 cells (DC3F/9-OHE cells) the resistance of which to the cytotoxic effect of intercalators and @entity2879 is associated with a reduced formation of protein-associated DNA strand breaks. In the present study, topoisomerases of these cells were compared to those of the parental sensitive cells (DC3F). @entity1219 extracts (0.35 M) of isolated DC3F/9-OHE nuclei did not form @entity5256 -induced DNA-protein linking, whereas DC3F nuclear extracts did. In addition, DC3F/9-OHE nuclear extract had an unusually high level of DNA linking activity in the absence of @entity5256 . Topoisomerases II from DC3F/9-OHE and DC3F nuclei appeared similar qualitatively. DC3F/9-OHE nuclear extract had approximately twice less topoisomerase II molecules than did DC3F nuclear extract but similar topoisomerase II activity. Topoisomerase I activities appeared also similar in sensitive and resistant cells. However, part of DC3F/9-OHE topoisomerase I copurified with a DNA linking activity which was not present in DC3F nuclei. This unusual DNA linking activity was not sensitive to the stimulatory effect of @entity5256 .
