DNA topoisomerase inhibitors induce reversible senescence in normal human fibroblasts

Biochem Biophys Res Commun. 1998 Dec 30;253(3):667-71. doi: 10.1006/bbrc.1998.9832.

Abstract

Inhibitors of DNA topoisomerases I and II induced arrest in cell division in normal human fibroblasts depending on cell divisions. Arrested cells showed morphology similar to those of normally senesced cells and strongly induced senescence-associated beta-galactosidase. In these cells, p16ink4a was upregulated, whereas p21waf1 or p53 was not altered. Upon removal of the inhibitors, the cells resumed growth but their cumulative population doublings were reduced dose dependently. Accelerated telomere shortening was not observed in the arrested cells. These results suggest that DNA topoisomerase inhibitors are efficient and reversible inducers of premature senescence in normal human cells.

MeSH terms

  • Cellular Senescence*
  • Cyclin-Dependent Kinase Inhibitor p16
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclins / metabolism
  • Fibroblasts / drug effects
  • Humans
  • Telomere / metabolism
  • Topoisomerase I Inhibitors*
  • Topoisomerase II Inhibitors*
  • Tumor Suppressor Protein p53 / metabolism

Substances

  • CDKN1A protein, human
  • Cyclin-Dependent Kinase Inhibitor p16
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclins
  • Topoisomerase I Inhibitors
  • Topoisomerase II Inhibitors
  • Tumor Suppressor Protein p53