Significance of the response of quiescent cell populations within solid tumors in cancer therapy

J Radiat Res. 2002 Mar;43(1):11-25. doi: 10.1269/jrr.43.11.

Abstract

In analyzing the response of quiescent (Q) cells in solid tumors, we have developed a combined method with a micronucleus (MN) assay and the identification of proliferating (P) cells by 5-bromo-2'-deoxyuridine (BrdU) and an anti-BrdU monoclonal antibody. Using this method, the responses of Q tumor cells as well as total tumor (P + Q) cells within murine solid tumors to various DNA-damaging treatments were evaluated. Based on this evaluation, combining with tirapazamine, a well-known bioreductive agent, and/or heat treatment at mild temperatures was thought to be a promising modality for cancer therapy in terms of conventional anticancer treatment-resistant Q cell control. Recently, our method for detecting the Q-cell response using P cell labeling with BrdU and the MN frequency assay was also shown to be applicable to an apoptosis detection assay. Meanwhile, our method for detecting the intratumor Q-cell response was also applicable toward high linear energy transfer radiation, including reactor neutrons. Thus, using our method, a new neutron capture compound that has the potential to be distributed in neutron capture therapy-resistant intratumor Q cell populations is now under development.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / radiation effects
  • Boron Neutron Capture Therapy
  • Bromodeoxyuridine / metabolism
  • Cell Division
  • DNA Damage
  • Humans
  • Interphase
  • Mice
  • Micronucleus Tests
  • Neoplasms / metabolism
  • Neoplasms / pathology
  • Neoplasms / radiotherapy
  • Neoplasms, Experimental / metabolism
  • Neoplasms, Experimental / pathology*
  • Neoplasms, Experimental / radiotherapy*

Substances

  • Bromodeoxyuridine