In vitro and in vivo 31P nuclear magnetic resonance measurements of metabolic changes post radiation

Umar Mahmood, Alan A. Alfieri, Douglas Ballon, Frank Traganos, Jason A. Koutcher

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

Radiation-induced metabolic changes previously observed in tumors using phosphorus nuclear magnetic resonance spectroscopy include changes in the relative amounts of the phospholipid precursors phosphoethanolamine and phosphocholine, increases in membrane catabolites, and increases in energy status. To elucidate the degree to which these in vivo alterations are a result of intrinsic cellular changes versus radiation-induced systemic effects, the Radiation-Induced Fibrosarcoma-1 tumor model was studied before and over the course of 7 days after a single dose of 17 Gy. In vivo studies were performed with tumors implanted in C3H/He mice; in vitro studies used cells that were perfused in agarose gel threads after being grown, radiated, and maintained in monolayer. The statistically significant increases in the downfield component of the phosphomonoester peak, which consists primarily of phosphoethanolamine, compared to the upfield component, phosphocholine, were qualitatively similar in vivo and in vitro post radiation. Statistically significant increases in the membrane catabolite glycerophosphocholine, a phosphodiester, were also observed in both tumors and cell culture after irradiation, with a greater percentage change in vitro. This suggests that changes in the phosphomonoester and phosphodiester concentrations are primarily an intrinsic effect of radiation on cellular metabolism, modulated to a lesser degree by systemic effects. In contrast, the statistically significant increases in energy status after the 17-Gy dose showed markedly different temporal responses in the two systems. Therefore, energy status changes observed in vivo are due largely to systemic changes, such as changes in blood flow. Flow cytometry data obtained from the cultured cells showed a sustained increase in the G2-M fraction starting at 24 h, the first time point measured after irradiation, which continued for the 7 days studied post radiation. These data indicate that the in vivo changes detected by nuclear magnetic resonance in phospholipid precursors and catabolites occur directly at the cellular level and may reflect cell death or growth inhibition after antineoplastic therapy.

Original languageEnglish (US)
Pages (from-to)1248-1254
Number of pages7
JournalCancer Research
Volume55
Issue number6
StatePublished - Mar 15 1995
Externally publishedYes

Fingerprint

Magnetic Resonance Spectroscopy
Radiation
Phosphorylcholine
Radiation Effects
Neoplasms
Phospholipids
Membranes
Inbred C3H Mouse
Fibrosarcoma
Antineoplastic Agents
Sepharose
Phosphorus
Cultured Cells
Flow Cytometry
Cell Death
Cell Culture Techniques
Gels
In Vitro Techniques
Growth
phosphorylethanolamine

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Mahmood, U., Alfieri, A. A., Ballon, D., Traganos, F., & Koutcher, J. A. (1995). In vitro and in vivo 31P nuclear magnetic resonance measurements of metabolic changes post radiation. Cancer Research, 55(6), 1248-1254.

In vitro and in vivo 31P nuclear magnetic resonance measurements of metabolic changes post radiation. / Mahmood, Umar; Alfieri, Alan A.; Ballon, Douglas; Traganos, Frank; Koutcher, Jason A.

In: Cancer Research, Vol. 55, No. 6, 15.03.1995, p. 1248-1254.

Research output: Contribution to journalArticle

Mahmood, U, Alfieri, AA, Ballon, D, Traganos, F & Koutcher, JA 1995, 'In vitro and in vivo 31P nuclear magnetic resonance measurements of metabolic changes post radiation', Cancer Research, vol. 55, no. 6, pp. 1248-1254.
Mahmood U, Alfieri AA, Ballon D, Traganos F, Koutcher JA. In vitro and in vivo 31P nuclear magnetic resonance measurements of metabolic changes post radiation. Cancer Research. 1995 Mar 15;55(6):1248-1254.
Mahmood, Umar ; Alfieri, Alan A. ; Ballon, Douglas ; Traganos, Frank ; Koutcher, Jason A. / In vitro and in vivo 31P nuclear magnetic resonance measurements of metabolic changes post radiation. In: Cancer Research. 1995 ; Vol. 55, No. 6. pp. 1248-1254.
@article{12a6e0d3f7664c838e1bb0cff68b33e5,
title = "In vitro and in vivo 31P nuclear magnetic resonance measurements of metabolic changes post radiation",
abstract = "Radiation-induced metabolic changes previously observed in tumors using phosphorus nuclear magnetic resonance spectroscopy include changes in the relative amounts of the phospholipid precursors phosphoethanolamine and phosphocholine, increases in membrane catabolites, and increases in energy status. To elucidate the degree to which these in vivo alterations are a result of intrinsic cellular changes versus radiation-induced systemic effects, the Radiation-Induced Fibrosarcoma-1 tumor model was studied before and over the course of 7 days after a single dose of 17 Gy. In vivo studies were performed with tumors implanted in C3H/He mice; in vitro studies used cells that were perfused in agarose gel threads after being grown, radiated, and maintained in monolayer. The statistically significant increases in the downfield component of the phosphomonoester peak, which consists primarily of phosphoethanolamine, compared to the upfield component, phosphocholine, were qualitatively similar in vivo and in vitro post radiation. Statistically significant increases in the membrane catabolite glycerophosphocholine, a phosphodiester, were also observed in both tumors and cell culture after irradiation, with a greater percentage change in vitro. This suggests that changes in the phosphomonoester and phosphodiester concentrations are primarily an intrinsic effect of radiation on cellular metabolism, modulated to a lesser degree by systemic effects. In contrast, the statistically significant increases in energy status after the 17-Gy dose showed markedly different temporal responses in the two systems. Therefore, energy status changes observed in vivo are due largely to systemic changes, such as changes in blood flow. Flow cytometry data obtained from the cultured cells showed a sustained increase in the G2-M fraction starting at 24 h, the first time point measured after irradiation, which continued for the 7 days studied post radiation. These data indicate that the in vivo changes detected by nuclear magnetic resonance in phospholipid precursors and catabolites occur directly at the cellular level and may reflect cell death or growth inhibition after antineoplastic therapy.",
author = "Umar Mahmood and Alfieri, {Alan A.} and Douglas Ballon and Frank Traganos and Koutcher, {Jason A.}",
year = "1995",
month = "3",
day = "15",
language = "English (US)",
volume = "55",
pages = "1248--1254",
journal = "Journal of Cancer Research",
issn = "0008-5472",
publisher = "American Association for Cancer Research Inc.",
number = "6",

}

TY - JOUR

T1 - In vitro and in vivo 31P nuclear magnetic resonance measurements of metabolic changes post radiation

AU - Mahmood, Umar

AU - Alfieri, Alan A.

AU - Ballon, Douglas

AU - Traganos, Frank

AU - Koutcher, Jason A.

PY - 1995/3/15

Y1 - 1995/3/15

N2 - Radiation-induced metabolic changes previously observed in tumors using phosphorus nuclear magnetic resonance spectroscopy include changes in the relative amounts of the phospholipid precursors phosphoethanolamine and phosphocholine, increases in membrane catabolites, and increases in energy status. To elucidate the degree to which these in vivo alterations are a result of intrinsic cellular changes versus radiation-induced systemic effects, the Radiation-Induced Fibrosarcoma-1 tumor model was studied before and over the course of 7 days after a single dose of 17 Gy. In vivo studies were performed with tumors implanted in C3H/He mice; in vitro studies used cells that were perfused in agarose gel threads after being grown, radiated, and maintained in monolayer. The statistically significant increases in the downfield component of the phosphomonoester peak, which consists primarily of phosphoethanolamine, compared to the upfield component, phosphocholine, were qualitatively similar in vivo and in vitro post radiation. Statistically significant increases in the membrane catabolite glycerophosphocholine, a phosphodiester, were also observed in both tumors and cell culture after irradiation, with a greater percentage change in vitro. This suggests that changes in the phosphomonoester and phosphodiester concentrations are primarily an intrinsic effect of radiation on cellular metabolism, modulated to a lesser degree by systemic effects. In contrast, the statistically significant increases in energy status after the 17-Gy dose showed markedly different temporal responses in the two systems. Therefore, energy status changes observed in vivo are due largely to systemic changes, such as changes in blood flow. Flow cytometry data obtained from the cultured cells showed a sustained increase in the G2-M fraction starting at 24 h, the first time point measured after irradiation, which continued for the 7 days studied post radiation. These data indicate that the in vivo changes detected by nuclear magnetic resonance in phospholipid precursors and catabolites occur directly at the cellular level and may reflect cell death or growth inhibition after antineoplastic therapy.

AB - Radiation-induced metabolic changes previously observed in tumors using phosphorus nuclear magnetic resonance spectroscopy include changes in the relative amounts of the phospholipid precursors phosphoethanolamine and phosphocholine, increases in membrane catabolites, and increases in energy status. To elucidate the degree to which these in vivo alterations are a result of intrinsic cellular changes versus radiation-induced systemic effects, the Radiation-Induced Fibrosarcoma-1 tumor model was studied before and over the course of 7 days after a single dose of 17 Gy. In vivo studies were performed with tumors implanted in C3H/He mice; in vitro studies used cells that were perfused in agarose gel threads after being grown, radiated, and maintained in monolayer. The statistically significant increases in the downfield component of the phosphomonoester peak, which consists primarily of phosphoethanolamine, compared to the upfield component, phosphocholine, were qualitatively similar in vivo and in vitro post radiation. Statistically significant increases in the membrane catabolite glycerophosphocholine, a phosphodiester, were also observed in both tumors and cell culture after irradiation, with a greater percentage change in vitro. This suggests that changes in the phosphomonoester and phosphodiester concentrations are primarily an intrinsic effect of radiation on cellular metabolism, modulated to a lesser degree by systemic effects. In contrast, the statistically significant increases in energy status after the 17-Gy dose showed markedly different temporal responses in the two systems. Therefore, energy status changes observed in vivo are due largely to systemic changes, such as changes in blood flow. Flow cytometry data obtained from the cultured cells showed a sustained increase in the G2-M fraction starting at 24 h, the first time point measured after irradiation, which continued for the 7 days studied post radiation. These data indicate that the in vivo changes detected by nuclear magnetic resonance in phospholipid precursors and catabolites occur directly at the cellular level and may reflect cell death or growth inhibition after antineoplastic therapy.

UR - http://www.scopus.com/inward/record.url?scp=0028986939&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0028986939&partnerID=8YFLogxK

M3 - Article

VL - 55

SP - 1248

EP - 1254

JO - Journal of Cancer Research

JF - Journal of Cancer Research

SN - 0008-5472

IS - 6

ER -