Effect of DNA topoisomerase I inhibitor, 10-hydroxycamptothecin, on the structure and function of nuclei and nuclear matrix in bladder carcinoma MBT-2 cells

Y. H. Ling, R. Perez-Soler, M. T. Tseng

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

The effects of 10-hydroxycamptothecin (HCPT), a DNA topoisomerase I inhibitor, on the structure of nuclei and nuclear matrix and new DNA replication was investigated in murine bladder carcinoma MBT-2 cells. Following 10-30 min exposure of exponentially growing cells to 10-50 μM HCPT, the rate of 2 min pulse-labeling with [3H]thymidine in whole nuclei, nonmatrix, and matrix fractions was markedly decreased in a concentration- and time-dependent manner. Reduction was highest in the nuclear matrix. After treatment of cultures with 50 μM HCPT for 10 min, inhibition of DNA synthesis was 60% in the nuclear matrix and 27% in the low-salt extract fraction tended to be stimulated after drug treatment. SDS-PAGE analysis of [35S]methionine labeled proteins indicated that 50 μM HCPT decreased protein synthesis in the matrix and other nuclear subfractions. HCPT-induced ultrastructural changes in nuclei and nuclear matrix were similar to those typically associated with lesions of DNA replication or RNA transcription.

Original languageEnglish (US)
Pages (from-to)1613-1617
Number of pages5
JournalAnticancer Research
Volume13
Issue number5 A
StatePublished - Jan 1 1993
Externally publishedYes

Keywords

  • 10-hydroxycamptothecin
  • Bladder carcinoma cells
  • DNA topoisomerase I inhibitor
  • Nuclear matrix
  • Nucleus

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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