Supraadditive apoptotic response of R3327-G rat prostate tumors to androgen ablation and radiation

Daryl Lim Joon, Masatoshi Hasegawa, Charles Sikes, Vincent S. Khoo, Nicholas H A Terry, Gunar K. Zagars, Marvin L. Meistrich, Alan Pollack

Research output: Contribution to journalArticle

123 Citations (Scopus)

Abstract

Purpose: Androgen ablation is often combined with radiation in the treatment of patients with prostate cancer, yet, the optimal sequencing and the mechanisms governing the interaction are not understood. The objectives were to determine if cell killing via apoptosis is enhanced when the combined treatment is administered and to define the relationship of changes in this form of cell killing to tumor volume growth delay. Materials and Methods: Dunning R3327-G rat prostate tumors, grown in the flanks of Copenhagen rats, were used at a volume of approximately 1 cc. Androgen ablation was initiated by castration, and androgen restoration was achieved with 0.5 cm silastic tube implants containing testosterone. 60Co was used for irradiation. The terminal deoxynucleotidyl transferase (TUNEL) histochemical assay was used to quantify apoptosis. Results: Tumors from intact and castrate unirradiated control rats had average apoptotic indices (percent of apoptotic cells) of 0.4 and 1.0%, respectively. The apoptotic index varied only slightly over time (3 h to 28 days) after castration (range 0.75-1.43%). Irradiation of intact rats to 7 Gy resulted in a peak apoptotic response at 6 h of 2.3%. A supraadditive apoptotic response was seen when castration was initiated 3 days prior to 7 Gy radiation, with peak levels of about 10.1%. When the radiation was administered at increasing times beyond 3 days after castration, the apoptotic response gradually diminished and was back to levels seen in intact rats by 28 days after castration. Tumor volume growth delay studies were consistent with, but not conclusive proof of, a supraadditive effect when the combination was used. Discussion: A supraadditive apoptotic response was seen when androgen ablation and radiation were used to treat androgen sensitive R3327-G rat prostate tumors. This supraadditive effect was dependent on the timing of the two treatments. Further studies are required to more fully define the optimal timing and administration of androgen ablation and radiation.

Original languageEnglish
Pages (from-to)1071-1077
Number of pages7
JournalInternational Journal of Radiation Oncology Biology Physics
Volume38
Issue number5
DOIs
StatePublished - Jul 15 1997
Externally publishedYes

Fingerprint

Castration
Androgens
ablation
rats
Prostate
tumors
Radiation
radiation
Neoplasms
apoptosis
Tumor Burden
time measurement
Apoptosis
Radiation Dosage
irradiation
sequencing
DNA Nucleotidylexotransferase
In Situ Nick-End Labeling
Growth
restoration

Keywords

  • Androgen ablation
  • Apoptosis
  • Prostate cancer
  • Radiation

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Radiation

Cite this

Supraadditive apoptotic response of R3327-G rat prostate tumors to androgen ablation and radiation. / Lim Joon, Daryl; Hasegawa, Masatoshi; Sikes, Charles; Khoo, Vincent S.; Terry, Nicholas H A; Zagars, Gunar K.; Meistrich, Marvin L.; Pollack, Alan.

In: International Journal of Radiation Oncology Biology Physics, Vol. 38, No. 5, 15.07.1997, p. 1071-1077.

Research output: Contribution to journalArticle

Lim Joon, Daryl ; Hasegawa, Masatoshi ; Sikes, Charles ; Khoo, Vincent S. ; Terry, Nicholas H A ; Zagars, Gunar K. ; Meistrich, Marvin L. ; Pollack, Alan. / Supraadditive apoptotic response of R3327-G rat prostate tumors to androgen ablation and radiation. In: International Journal of Radiation Oncology Biology Physics. 1997 ; Vol. 38, No. 5. pp. 1071-1077.
@article{501e468a665e4f379c7ff2b785025491,
title = "Supraadditive apoptotic response of R3327-G rat prostate tumors to androgen ablation and radiation",
abstract = "Purpose: Androgen ablation is often combined with radiation in the treatment of patients with prostate cancer, yet, the optimal sequencing and the mechanisms governing the interaction are not understood. The objectives were to determine if cell killing via apoptosis is enhanced when the combined treatment is administered and to define the relationship of changes in this form of cell killing to tumor volume growth delay. Materials and Methods: Dunning R3327-G rat prostate tumors, grown in the flanks of Copenhagen rats, were used at a volume of approximately 1 cc. Androgen ablation was initiated by castration, and androgen restoration was achieved with 0.5 cm silastic tube implants containing testosterone. 60Co was used for irradiation. The terminal deoxynucleotidyl transferase (TUNEL) histochemical assay was used to quantify apoptosis. Results: Tumors from intact and castrate unirradiated control rats had average apoptotic indices (percent of apoptotic cells) of 0.4 and 1.0{\%}, respectively. The apoptotic index varied only slightly over time (3 h to 28 days) after castration (range 0.75-1.43{\%}). Irradiation of intact rats to 7 Gy resulted in a peak apoptotic response at 6 h of 2.3{\%}. A supraadditive apoptotic response was seen when castration was initiated 3 days prior to 7 Gy radiation, with peak levels of about 10.1{\%}. When the radiation was administered at increasing times beyond 3 days after castration, the apoptotic response gradually diminished and was back to levels seen in intact rats by 28 days after castration. Tumor volume growth delay studies were consistent with, but not conclusive proof of, a supraadditive effect when the combination was used. Discussion: A supraadditive apoptotic response was seen when androgen ablation and radiation were used to treat androgen sensitive R3327-G rat prostate tumors. This supraadditive effect was dependent on the timing of the two treatments. Further studies are required to more fully define the optimal timing and administration of androgen ablation and radiation.",
keywords = "Androgen ablation, Apoptosis, Prostate cancer, Radiation",
author = "{Lim Joon}, Daryl and Masatoshi Hasegawa and Charles Sikes and Khoo, {Vincent S.} and Terry, {Nicholas H A} and Zagars, {Gunar K.} and Meistrich, {Marvin L.} and Alan Pollack",
year = "1997",
month = "7",
day = "15",
doi = "10.1016/S0360-3016(97)00303-9",
language = "English",
volume = "38",
pages = "1071--1077",
journal = "International Journal of Radiation Oncology Biology Physics",
issn = "0360-3016",
publisher = "Elsevier Inc.",
number = "5",

}

TY - JOUR

T1 - Supraadditive apoptotic response of R3327-G rat prostate tumors to androgen ablation and radiation

AU - Lim Joon, Daryl

AU - Hasegawa, Masatoshi

AU - Sikes, Charles

AU - Khoo, Vincent S.

AU - Terry, Nicholas H A

AU - Zagars, Gunar K.

AU - Meistrich, Marvin L.

AU - Pollack, Alan

PY - 1997/7/15

Y1 - 1997/7/15

N2 - Purpose: Androgen ablation is often combined with radiation in the treatment of patients with prostate cancer, yet, the optimal sequencing and the mechanisms governing the interaction are not understood. The objectives were to determine if cell killing via apoptosis is enhanced when the combined treatment is administered and to define the relationship of changes in this form of cell killing to tumor volume growth delay. Materials and Methods: Dunning R3327-G rat prostate tumors, grown in the flanks of Copenhagen rats, were used at a volume of approximately 1 cc. Androgen ablation was initiated by castration, and androgen restoration was achieved with 0.5 cm silastic tube implants containing testosterone. 60Co was used for irradiation. The terminal deoxynucleotidyl transferase (TUNEL) histochemical assay was used to quantify apoptosis. Results: Tumors from intact and castrate unirradiated control rats had average apoptotic indices (percent of apoptotic cells) of 0.4 and 1.0%, respectively. The apoptotic index varied only slightly over time (3 h to 28 days) after castration (range 0.75-1.43%). Irradiation of intact rats to 7 Gy resulted in a peak apoptotic response at 6 h of 2.3%. A supraadditive apoptotic response was seen when castration was initiated 3 days prior to 7 Gy radiation, with peak levels of about 10.1%. When the radiation was administered at increasing times beyond 3 days after castration, the apoptotic response gradually diminished and was back to levels seen in intact rats by 28 days after castration. Tumor volume growth delay studies were consistent with, but not conclusive proof of, a supraadditive effect when the combination was used. Discussion: A supraadditive apoptotic response was seen when androgen ablation and radiation were used to treat androgen sensitive R3327-G rat prostate tumors. This supraadditive effect was dependent on the timing of the two treatments. Further studies are required to more fully define the optimal timing and administration of androgen ablation and radiation.

AB - Purpose: Androgen ablation is often combined with radiation in the treatment of patients with prostate cancer, yet, the optimal sequencing and the mechanisms governing the interaction are not understood. The objectives were to determine if cell killing via apoptosis is enhanced when the combined treatment is administered and to define the relationship of changes in this form of cell killing to tumor volume growth delay. Materials and Methods: Dunning R3327-G rat prostate tumors, grown in the flanks of Copenhagen rats, were used at a volume of approximately 1 cc. Androgen ablation was initiated by castration, and androgen restoration was achieved with 0.5 cm silastic tube implants containing testosterone. 60Co was used for irradiation. The terminal deoxynucleotidyl transferase (TUNEL) histochemical assay was used to quantify apoptosis. Results: Tumors from intact and castrate unirradiated control rats had average apoptotic indices (percent of apoptotic cells) of 0.4 and 1.0%, respectively. The apoptotic index varied only slightly over time (3 h to 28 days) after castration (range 0.75-1.43%). Irradiation of intact rats to 7 Gy resulted in a peak apoptotic response at 6 h of 2.3%. A supraadditive apoptotic response was seen when castration was initiated 3 days prior to 7 Gy radiation, with peak levels of about 10.1%. When the radiation was administered at increasing times beyond 3 days after castration, the apoptotic response gradually diminished and was back to levels seen in intact rats by 28 days after castration. Tumor volume growth delay studies were consistent with, but not conclusive proof of, a supraadditive effect when the combination was used. Discussion: A supraadditive apoptotic response was seen when androgen ablation and radiation were used to treat androgen sensitive R3327-G rat prostate tumors. This supraadditive effect was dependent on the timing of the two treatments. Further studies are required to more fully define the optimal timing and administration of androgen ablation and radiation.

KW - Androgen ablation

KW - Apoptosis

KW - Prostate cancer

KW - Radiation

UR - http://www.scopus.com/inward/record.url?scp=0030805690&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0030805690&partnerID=8YFLogxK

U2 - 10.1016/S0360-3016(97)00303-9

DO - 10.1016/S0360-3016(97)00303-9

M3 - Article

C2 - 9276374

AN - SCOPUS:0030805690

VL - 38

SP - 1071

EP - 1077

JO - International Journal of Radiation Oncology Biology Physics

JF - International Journal of Radiation Oncology Biology Physics

SN - 0360-3016

IS - 5

ER -