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Polyploidy induction as a consequence of topoisomerase inhibition. A flow cytometric assessment.

Publication ,  Journal Article
Zucker, RM; Adams, DJ; Bair, KW; Elstein, KH
Published in: Biochem Pharmacol
November 6, 1991

Following recovery from a 4-hr exposure to clinically achievable concentrations of the topoisomerase II inhibitors Adriamycin, teniposide, or amsacrine or the putative topoisomerase II inhibitor crisnatol, murine erythroleukemic cells remained viable for up to 48 hr, but did not proliferate. Cell cycle analysis after a 24-hr recovery revealed blocks in G2 (4N DNA) or greater than G2 (up to 8N DNA) polyploid stages. The relative percentages of cells in either stage was a function of drug concentration and cell cycle stage at time of exposure: typically, cells exposed during S phase became blocked in G2, whereas those exposed during G2/M progressed into greater than G2 polyploid stages. G2-blocked cells exhibited a 2- to 3-fold increase in nuclear protein content and cellular/nuclear volume (i.e. unbalanced growth) and approximately 5% more DNA stainability (as a consequence of nuclear conformational changes rather than redundant DNA synthesis). In all cases, at the drug concentrations studied, mitotic figures were absent and G2 and greater than G2 blocks were irreversible, indicating that the mechanism of polyploidy induction differs from that of microtubule inhibitors. These findings suggest that although topoisomerase inhibitors interfere with DNA synthesis in the S phase, their induction of greater than G2 polyploid blocks may involve direct or indirect inhibition of chromosome condensation.

Duke Scholars

Published In

Biochem Pharmacol

DOI

ISSN

0006-2952

Publication Date

November 6, 1991

Volume

42

Issue

11

Start / End Page

2199 / 2208

Location

England

Related Subject Headings

  • Tumor Cells, Cultured
  • Topoisomerase II Inhibitors
  • Topoisomerase I Inhibitors
  • Thymidine
  • Teniposide
  • Polyploidy
  • Pharmacology & Pharmacy
  • Mice
  • Leukemia, Erythroblastic, Acute
  • G2 Phase
 

Citation

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Zucker, R. M., Adams, D. J., Bair, K. W., & Elstein, K. H. (1991). Polyploidy induction as a consequence of topoisomerase inhibition. A flow cytometric assessment. Biochem Pharmacol, 42(11), 2199–2208. https://doi.org/10.1016/0006-2952(91)90357-b
Zucker, R. M., D. J. Adams, K. W. Bair, and K. H. Elstein. “Polyploidy induction as a consequence of topoisomerase inhibition. A flow cytometric assessment.Biochem Pharmacol 42, no. 11 (November 6, 1991): 2199–2208. https://doi.org/10.1016/0006-2952(91)90357-b.
Zucker RM, Adams DJ, Bair KW, Elstein KH. Polyploidy induction as a consequence of topoisomerase inhibition. A flow cytometric assessment. Biochem Pharmacol. 1991 Nov 6;42(11):2199–208.
Zucker, R. M., et al. “Polyploidy induction as a consequence of topoisomerase inhibition. A flow cytometric assessment.Biochem Pharmacol, vol. 42, no. 11, Nov. 1991, pp. 2199–208. Pubmed, doi:10.1016/0006-2952(91)90357-b.
Zucker RM, Adams DJ, Bair KW, Elstein KH. Polyploidy induction as a consequence of topoisomerase inhibition. A flow cytometric assessment. Biochem Pharmacol. 1991 Nov 6;42(11):2199–2208.
Journal cover image

Published In

Biochem Pharmacol

DOI

ISSN

0006-2952

Publication Date

November 6, 1991

Volume

42

Issue

11

Start / End Page

2199 / 2208

Location

England

Related Subject Headings

  • Tumor Cells, Cultured
  • Topoisomerase II Inhibitors
  • Topoisomerase I Inhibitors
  • Thymidine
  • Teniposide
  • Polyploidy
  • Pharmacology & Pharmacy
  • Mice
  • Leukemia, Erythroblastic, Acute
  • G2 Phase