Quiescence in R3327-G Rat prostate tumors after androgen ablation

Alan Pollack, Daryl Lim Joon, Catherine S. Wu, Charles Sikes, Masatoshi Hasegawa, Nicholas H.A. Terry, R. Allen White, Gunar K. Zagars, Marvin L. Meistrich

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31 Scopus citations

Abstract

Androgen ablation is frequently used in conjunction with radiotherapy in the treatment of high-risk prostate cancer. Androgen ablation-induced cell kinetic changes could result in sub-additive (increased quiescence) or supra- additive (reduction in repopulation) interactions with radiotherapy. The cell kinetic changes were studied in R3327-G Dunning rat prostate tumors grown in vivo using double thymidine analogue labeling and flow cytometry, the terminal deoxynucleotidyl transferase-mediated nick end labeling assay for apoptosis, and measurements of tumor cell numbers. Tumors grown in intact and castrate male rats were continuously labeled for various periods of time with chlorodeoxyuridine and pulse-labeled with iododeoxyuridine 8 h before tumor removal. Androgen ablation resulted in a maximal reduction in labeling index (10 to 1.6%) and an increase in potential doubling time (Tpot; 6-42 days) within 3 days, which was related to a reduction in growth fraction (65% to < 10%). In contrast, the length of S-phase was minimally altered (19 to 23 h). The response to androgen ablution involved little apoptosis and no necrosis, and Tpot was approximately the same as the tumor volume doubling time. Hence, the increase in Tpot was mainly the result of a shift to quiescence, and this shift occurred with minimal cell loss. Because quiescence is usually associated with radioresistance, these cell kinetic changes suggest that a sub-additive interaction may occur for some prostate cancers when androgen ablution and irradiation are given together.

Original languageEnglish (US)
Pages (from-to)2493-2500
Number of pages8
JournalCancer Research
Volume57
Issue number12
StatePublished - Jun 15 1997
Externally publishedYes

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ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Pollack, A., Lim Joon, D., Wu, C. S., Sikes, C., Hasegawa, M., Terry, N. H. A., White, R. A., Zagars, G. K., & Meistrich, M. L. (1997). Quiescence in R3327-G Rat prostate tumors after androgen ablation. Cancer Research, 57(12), 2493-2500.