The macrocyclic lactone protein kinase C activator, bryostatin 1, either alone, or in conjunction with recombinant murine granulocyte-macrophage colony-Stimulating factor, protects Balb/c and C3H/HeN mice from the lethal in vivo effects of ionizing radiation

Steven Grant, Rebecca Traylor, George Pettit, Peck Sun Lin

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Abstract

We have examined the in vivo radioprotective effects of the macrocyclic lactone protein kinase C (PK-C) activator, bryostatin 1, administered either alone or in conjunction with recombinant murine granulocyte-macrophage colonystimulating factor (rmGM-CSF), in Balb/c and C3H/HeN mice subjected to lethal total body irradiation (TBI). When administered alone on a divided dose schedule (24 hours and 30 minutes before TBI), rmGM-CSF (20 μg/kg) was ineffective in increasing survival in either strain. However, in Balb/c mice, bryostatin 1 alone (1 μg) permitted the long-term survival (60 days) of 70% of the animals following TBI, and 80% when administered in conjunction with rmGM-CSF. Bryostatin 1 administered alone according to this schedule exerted minimal radioprotective effects in C3H/ HeN mice, but, when combined with a subeffective dose of rmGM-CSF, allowed 50% of the animals to survive. Treatment of Balb/c mice with bryostatin 1 administered as a single dose 4 hours before TBI resulted in a 20% survival rate, and 45% when administered with rmGM-CSF; corresponding values for the C3H/HeN strain were 60% and 40%, respectively. Lastly, the survival rates of Balb/c mice treated with bryostatin 1 administered as a single dose 4 hours following TBI was 20%, and 25% with rmGM-CSF; corresponding values were 50% and 25% for C3H/HeN mice. These findings indicate that the PK-C activator bryostatin 1 exhibits intrinsic in vivo radioprotective effects in lethally irradiated Balb/c and C3H/HeN mice, and may, under some circumstances, augment the radioprotective capacity of rmGM-CSF. They also underscore the critical role that strain differences and scheduling considerations play in determining the in vivo radioprotective capacity of bryostatin 1, as well as its interactions with rmGM-CSF.

Original languageEnglish (US)
Pages (from-to)663-667
Number of pages5
JournalBlood
Volume83
Issue number3
StatePublished - Feb 1 1994
Externally publishedYes

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Inbred C3H Mouse
Macrophages
Ionizing radiation
Lactones
Granulocyte-Macrophage Colony-Stimulating Factor
Ionizing Radiation
Granulocytes
Protein Kinase C
Whole-Body Irradiation
Irradiation
Dosimetry
Appointments and Schedules
Animals
bryostatin 1
Scheduling

ASJC Scopus subject areas

  • Hematology

Cite this

@article{2122e100e98a49cb8770475dd5bdf3f5,
title = "The macrocyclic lactone protein kinase C activator, bryostatin 1, either alone, or in conjunction with recombinant murine granulocyte-macrophage colony-Stimulating factor, protects Balb/c and C3H/HeN mice from the lethal in vivo effects of ionizing radiation",
abstract = "We have examined the in vivo radioprotective effects of the macrocyclic lactone protein kinase C (PK-C) activator, bryostatin 1, administered either alone or in conjunction with recombinant murine granulocyte-macrophage colonystimulating factor (rmGM-CSF), in Balb/c and C3H/HeN mice subjected to lethal total body irradiation (TBI). When administered alone on a divided dose schedule (24 hours and 30 minutes before TBI), rmGM-CSF (20 μg/kg) was ineffective in increasing survival in either strain. However, in Balb/c mice, bryostatin 1 alone (1 μg) permitted the long-term survival (60 days) of 70{\%} of the animals following TBI, and 80{\%} when administered in conjunction with rmGM-CSF. Bryostatin 1 administered alone according to this schedule exerted minimal radioprotective effects in C3H/ HeN mice, but, when combined with a subeffective dose of rmGM-CSF, allowed 50{\%} of the animals to survive. Treatment of Balb/c mice with bryostatin 1 administered as a single dose 4 hours before TBI resulted in a 20{\%} survival rate, and 45{\%} when administered with rmGM-CSF; corresponding values for the C3H/HeN strain were 60{\%} and 40{\%}, respectively. Lastly, the survival rates of Balb/c mice treated with bryostatin 1 administered as a single dose 4 hours following TBI was 20{\%}, and 25{\%} with rmGM-CSF; corresponding values were 50{\%} and 25{\%} for C3H/HeN mice. These findings indicate that the PK-C activator bryostatin 1 exhibits intrinsic in vivo radioprotective effects in lethally irradiated Balb/c and C3H/HeN mice, and may, under some circumstances, augment the radioprotective capacity of rmGM-CSF. They also underscore the critical role that strain differences and scheduling considerations play in determining the in vivo radioprotective capacity of bryostatin 1, as well as its interactions with rmGM-CSF.",
author = "Steven Grant and Rebecca Traylor and George Pettit and Lin, {Peck Sun}",
year = "1994",
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pages = "663--667",
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T1 - The macrocyclic lactone protein kinase C activator, bryostatin 1, either alone, or in conjunction with recombinant murine granulocyte-macrophage colony-Stimulating factor, protects Balb/c and C3H/HeN mice from the lethal in vivo effects of ionizing radiation

AU - Grant, Steven

AU - Traylor, Rebecca

AU - Pettit, George

AU - Lin, Peck Sun

PY - 1994/2/1

Y1 - 1994/2/1

N2 - We have examined the in vivo radioprotective effects of the macrocyclic lactone protein kinase C (PK-C) activator, bryostatin 1, administered either alone or in conjunction with recombinant murine granulocyte-macrophage colonystimulating factor (rmGM-CSF), in Balb/c and C3H/HeN mice subjected to lethal total body irradiation (TBI). When administered alone on a divided dose schedule (24 hours and 30 minutes before TBI), rmGM-CSF (20 μg/kg) was ineffective in increasing survival in either strain. However, in Balb/c mice, bryostatin 1 alone (1 μg) permitted the long-term survival (60 days) of 70% of the animals following TBI, and 80% when administered in conjunction with rmGM-CSF. Bryostatin 1 administered alone according to this schedule exerted minimal radioprotective effects in C3H/ HeN mice, but, when combined with a subeffective dose of rmGM-CSF, allowed 50% of the animals to survive. Treatment of Balb/c mice with bryostatin 1 administered as a single dose 4 hours before TBI resulted in a 20% survival rate, and 45% when administered with rmGM-CSF; corresponding values for the C3H/HeN strain were 60% and 40%, respectively. Lastly, the survival rates of Balb/c mice treated with bryostatin 1 administered as a single dose 4 hours following TBI was 20%, and 25% with rmGM-CSF; corresponding values were 50% and 25% for C3H/HeN mice. These findings indicate that the PK-C activator bryostatin 1 exhibits intrinsic in vivo radioprotective effects in lethally irradiated Balb/c and C3H/HeN mice, and may, under some circumstances, augment the radioprotective capacity of rmGM-CSF. They also underscore the critical role that strain differences and scheduling considerations play in determining the in vivo radioprotective capacity of bryostatin 1, as well as its interactions with rmGM-CSF.

AB - We have examined the in vivo radioprotective effects of the macrocyclic lactone protein kinase C (PK-C) activator, bryostatin 1, administered either alone or in conjunction with recombinant murine granulocyte-macrophage colonystimulating factor (rmGM-CSF), in Balb/c and C3H/HeN mice subjected to lethal total body irradiation (TBI). When administered alone on a divided dose schedule (24 hours and 30 minutes before TBI), rmGM-CSF (20 μg/kg) was ineffective in increasing survival in either strain. However, in Balb/c mice, bryostatin 1 alone (1 μg) permitted the long-term survival (60 days) of 70% of the animals following TBI, and 80% when administered in conjunction with rmGM-CSF. Bryostatin 1 administered alone according to this schedule exerted minimal radioprotective effects in C3H/ HeN mice, but, when combined with a subeffective dose of rmGM-CSF, allowed 50% of the animals to survive. Treatment of Balb/c mice with bryostatin 1 administered as a single dose 4 hours before TBI resulted in a 20% survival rate, and 45% when administered with rmGM-CSF; corresponding values for the C3H/HeN strain were 60% and 40%, respectively. Lastly, the survival rates of Balb/c mice treated with bryostatin 1 administered as a single dose 4 hours following TBI was 20%, and 25% with rmGM-CSF; corresponding values were 50% and 25% for C3H/HeN mice. These findings indicate that the PK-C activator bryostatin 1 exhibits intrinsic in vivo radioprotective effects in lethally irradiated Balb/c and C3H/HeN mice, and may, under some circumstances, augment the radioprotective capacity of rmGM-CSF. They also underscore the critical role that strain differences and scheduling considerations play in determining the in vivo radioprotective capacity of bryostatin 1, as well as its interactions with rmGM-CSF.

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