Mitoxantrone resistance in HL-60 leukemia cells: reduced nuclear topoisomerase II catalytic activity and drug-induced DNA cleavage in association with reduced expression of the topoisomerase II .beta. isoform

Biochemistry ◽  
1991 ◽  
Vol 30 (41) ◽  
pp. 9953-9961 ◽  
Author(s):  
W. Graydon Harker ◽  
D. Lynn Slade ◽  
Fred H. Drake ◽  
Ryan L. Parr
Keyword(s):  
Catalytic Activity ◽  
Dna Cleavage ◽  
Topoisomerase Ii ◽  
Leukemia Cells ◽  
Drug Induced ◽  
Topoisomerase Ii Beta

The effect of staurosporine on drug-induced, topoisomerase II-mediated DNA cleavage in human leukemia cells

1991 ◽  
Vol 29 (1) ◽  
pp. 48-52 ◽  
Author(s):  
Leonard A. Zwelling ◽  
Elizabeth Altschuler ◽  
Janice Mayes ◽  
Michael Hinds ◽  
Diana Chan
Keyword(s):  
Dna Cleavage ◽  
Topoisomerase Ii ◽  
Leukemia Cells ◽  
Human Leukemia ◽  
Drug Induced ◽  
Human Leukemia Cells

Effect of bryostatin 1 on drug-induced, topoisomerase II-mediated DNA cleavage and topoisomerase 11 gene expression in human leukemia cells

1991 ◽  
Vol 41 (5) ◽  
pp. 829-832 ◽  
Author(s):  
Leonard A. Zwelling ◽  
Diana Chan ◽  
Elizabeth Altschuler ◽  
Janice Mayes ◽  
Michael Hinds ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Cleavage ◽  
Topoisomerase Ii ◽  
Leukemia Cells ◽  
Human Leukemia ◽  
Bryostatin 1 ◽  
Drug Induced ◽  
Human Leukemia Cells

Altered catalytic activity of and DNA cleavage by DNA topoisomerase II from human leukemic cells selected for resistance to VM-26

Biochemistry ◽  
1988 ◽  
Vol 27 (24) ◽  
pp. 8861-8869 ◽  
Author(s):  
Mary K. Danks ◽  
Carla A. Schmidt ◽  
Margaret C. Cirtain ◽  
D. Parker Suttle ◽  
William T. Beck
Keyword(s):  
Catalytic Activity ◽  
Dna Cleavage ◽  
Topoisomerase Ii ◽  
Leukemic Cells ◽  
Dna Topoisomerase Ii ◽  
Dna Topoisomerase ◽  
Human Leukemic Cells

Altered DNA-cleavage activity of topoisomerase II from WEHI-3B leukemia cells with specific resistance to ciprofloxacin

2001 ◽  
Vol 12 (5) ◽  
pp. 441-451 ◽  
Author(s):  
Augusto Pessina ◽  
Alessandro Raimondi ◽  
Cristina Croera ◽  
Mara Acchini ◽  
Elisabetta Mineo ◽  
...  
Keyword(s):  
Dna Cleavage ◽  
Topoisomerase Ii ◽  
Specific Resistance ◽  
Leukemia Cells ◽  
Cleavage Activity ◽  
Dna Cleavage Activity

scholarly journals Topoisomerase-specific drug sensitivity in relation to cell cycle progression.

1987 ◽  
Vol 7 (9) ◽  
pp. 3119-3123 ◽  
Author(s):  
K C Chow ◽  
W E Ross
Keyword(s):  
Cell Cycle ◽  
Dna Cleavage ◽  
Cell Cycle Progression ◽  
Topoisomerase Ii ◽  
Drug Sensitivity ◽  
S Phase ◽  
Synthesis Inhibitor ◽  
Drug Induced ◽  
Cycle Progression ◽  
Serum Stimulation

The nuclear enzyme DNA topoisomerase II catalyzes the breakage and resealing of duplex DNA and plays an important role in several genetic processes. It also mediates the DNA cleavage activity and cytotoxicity of clinically important anticancer agents such as etoposide. We have examined the activity of topoisomerase II during the first cell cycle of quiescent BALB/c 3T3 cells following serum stimulation. Etoposide-mediated DNA break frequency in vivo was used as a parameter of topoisomerase II activity, and enzyme content was assayed by immunoblotting. Density-arrested A31 cells exhibited a much lower sensitivity to the effects of etoposide than did actively proliferating cells. Upon serum stimulation of the quiescent cells, however, there was a marked increase in drug sensitivity which began during S phase and reached its peak just before mitosis. Maximal drug sensitivity during this period was 2.5 times greater than that of log-phase cells. This increase in drug sensitivity was associated with an increase in intracellular topoisomerase II content as determined by immunoblotting. The induction of topoisomerase II-mediated drug sensitivity was aborted within 1 h of exposure of cells to the protein synthesis inhibitor cycloheximide, but the DNA synthesis inhibitor aphidicolin had no effect. In contrast to the sensitivity of cells to drug-induced DNA cleavage, maximal cytotoxicity occurred during S phase. A 3-h exposure to cycloheximide before etoposide treatment resulted in nearly complete loss of cytotoxicity. Our findings indicate that topoisomerase II activity fluctuates with cell cycle progression, with peak activity occurring during the G2 phase. This increase in topoisomerase II is protein synthesis dependent and may reflect a high rate of enzyme turnover. The dissociation between maximal drug-induced DNA cleavage and cytotoxicity indicates that the topoisomerase-mediated DNA breaks may be necessary but are not sufficient for cytotoxicity and that the other factors which are particularly expressed during S phase may be important as well.

Cell cycle stage-dependent variations in drug-induced topoisomerase II mediated DNA cleavage and cytotoxicity

Biochemistry ◽  
1987 ◽  
Vol 26 (14) ◽  
pp. 4338-4344 ◽  
Author(s):  
Elihu Estey ◽  
Ramesh C. Adlakha ◽  
Walter N. Hittelman ◽  
Leonard A. Zwelling
Keyword(s):  
Cell Cycle ◽  
Dna Cleavage ◽  
Topoisomerase Ii ◽  
Drug Induced ◽  
Cell Cycle Stage

Topoisomerase-specific drug sensitivity in relation to cell cycle progression

1987 ◽  
Vol 7 (9) ◽  
pp. 3119-3123
Author(s):  
K C Chow ◽  
W E Ross
Keyword(s):  
Cell Cycle ◽  
Dna Cleavage ◽  
Cell Cycle Progression ◽  
Topoisomerase Ii ◽  
Drug Sensitivity ◽  
S Phase ◽  
Synthesis Inhibitor ◽  
Drug Induced ◽  
Cycle Progression ◽  
Serum Stimulation

The nuclear enzyme DNA topoisomerase II catalyzes the breakage and resealing of duplex DNA and plays an important role in several genetic processes. It also mediates the DNA cleavage activity and cytotoxicity of clinically important anticancer agents such as etoposide. We have examined the activity of topoisomerase II during the first cell cycle of quiescent BALB/c 3T3 cells following serum stimulation. Etoposide-mediated DNA break frequency in vivo was used as a parameter of topoisomerase II activity, and enzyme content was assayed by immunoblotting. Density-arrested A31 cells exhibited a much lower sensitivity to the effects of etoposide than did actively proliferating cells. Upon serum stimulation of the quiescent cells, however, there was a marked increase in drug sensitivity which began during S phase and reached its peak just before mitosis. Maximal drug sensitivity during this period was 2.5 times greater than that of log-phase cells. This increase in drug sensitivity was associated with an increase in intracellular topoisomerase II content as determined by immunoblotting. The induction of topoisomerase II-mediated drug sensitivity was aborted within 1 h of exposure of cells to the protein synthesis inhibitor cycloheximide, but the DNA synthesis inhibitor aphidicolin had no effect. In contrast to the sensitivity of cells to drug-induced DNA cleavage, maximal cytotoxicity occurred during S phase. A 3-h exposure to cycloheximide before etoposide treatment resulted in nearly complete loss of cytotoxicity. Our findings indicate that topoisomerase II activity fluctuates with cell cycle progression, with peak activity occurring during the G2 phase. This increase in topoisomerase II is protein synthesis dependent and may reflect a high rate of enzyme turnover. The dissociation between maximal drug-induced DNA cleavage and cytotoxicity indicates that the topoisomerase-mediated DNA breaks may be necessary but are not sufficient for cytotoxicity and that the other factors which are particularly expressed during S phase may be important as well.

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