Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:5.99.1.2 (topoisomerase)
 9,166 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Using cultured V79 Chinese hamster cells, we found that novobiocin (or 2,4-dinitrophenol) can abrogate, almost completely, the cytotoxicity due to the topoisomerase II inhibitor amsacrine (mAMSA). V79 cells were sensitive to mAMSA killing at all stages in the cell cycle but mainly in S phase followed by late G1 phase; however, novo rescued cells of all ages. The properties of two kinds of radiation-sensitive Chinese hamster cells were also examined, i.e., the line of V79 cells that can be rescued by caffeine, designated S-10 (H. Utsumi and M.M. Elkind, Radiat. Res., 96: 348-358, 1983); and Chinese hamster ovary cells (P.A. Jeggo and L.M. Kemp, Mutat. Res., 112: 313-327, 1983) which are also sensitive to other DNA-damaging agents. As is the case for exposure to radiation, after mAMSA treatment caffeine rescued V79/S-10 cells. Although Jeggo's Chinese hamster ovary cells were more responsive to mAMSA, novo still abrogated mAMSA toxicity in the mutant cells as well as in the parental Chinese hamster ovary cells 2,4-Dinitrophenol acted similarly to novo with respect to mAMSA killing, but neither compound reduced the ATP content of V79 cells. We propose that one reason for the rescue from mAMSA killing of at least S-phase cells by novo or 2,4-dinitrophenol is their ability transiently to inhibit replicative DNA synthesis.
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PMID:Abrogation by novobiocin of cytotoxicity due to the topoisomerase II inhibitor amsacrine in Chinese hamster cells. 215 94

The effect of the ATP pool on the cytotoxic action of teniposide (VM-26) has been studied in mouse leukemia cells (L1210). L1210 cells in tissue culture were treated with VM-26 (10 microM) in the presence of DNP, an uncoupler of oxidative phosphorylation. The simultaneous treatment of DNP (1 mM) increased cell survival 100-200 fold. Pre- or post-treatment with DNP had little effect on cell survival. Other uncouplers and inhibitors of ATP synthesis had effects similar to DNP. The interference of DNP with the cytotoxic action of VM-26 was also seen with another topoisomerase II-targetting drug, m-AMSA, but not with the topoisomerase I-targetting drug camptothecin. Studies using either purified topoisomerase II or cultured mammalian cells had shown that DNP had little effect on the amount of cleavable complexes induced by VM-26. We propose that an ATP requiring process(es) which occurs subsequent to the formation of the cleavable complexes is involved in the cytotoxic action of topoisomerase II-targetting drugs.
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PMID:Involvement of intracellular ATP in cytotoxicity of topoisomerase II-targetting antitumor drugs. 281 29