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Elevations of DNA topoisomerase I catalytic activity and immunoprotein in human malignancies

I B Bronstein1, S Vorobyev, A Timofeev

  • 1Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia.

Oncology Research
|January 1, 1996
PubMed

Insights

Cancer drug sensitivity hinges on DNA topoisomerase I (topo I) levels. This study found higher topo I in many human tumors, suggesting potential sensitivity to topo I-targeting anticancer drugs.

Area of Science:

  • Biochemistry
  • Oncology
  • Molecular Biology

Background:

  • DNA topoisomerase I (topo I) is the target for camptothecin anticancer drugs.
  • Tumor cell sensitivity to these drugs correlates with topo I levels.
  • Information on topo I levels in human malignancies is limited.

Purpose of the Study:

  • To investigate topo I activity and protein levels in normal and cancerous human tissues.
  • To assess the relationship between topo I levels and tumor type.
  • To evaluate the potential of topo I levels as a predictor of drug sensitivity.

Main Methods:

  • Enzyme activity assays to measure topo I catalytic activity.
  • Western blot analysis to quantify topo I immunoprotein levels.
  • Flow cytometry to determine the percentage of cycling cells in neoplastic specimens.

Main Results:

  • Topo I activity was consistent in normal tissues (average 2.7 x 10^4 units/mg protein).
  • Topo I activity varied significantly in human malignancies, with some showing much higher levels (up to 160 x 10^4 units/mg protein).
  • Elevated topo I activity in tumors was attributed to increased topo I protein levels.

Conclusions:

  • Human malignancies exhibit variable, often elevated, levels of DNA topoisomerase I.
  • High topo I levels in tumors may indicate sensitivity to topo I-targeting anticancer therapies.
  • Further research is warranted to explore the clinical implications of topo I levels in cancer treatment.

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