Apoptosis, energy metabolism, and fraction of radiobiologically hypoxic cells: A study of human melanoma multicellular spheroids

E. K. Rofstad, K. Eide, R. Skøyum, M. E. Hystad, H. Lyng

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

The magnitude of the fraction of radiobiologically hypoxic cells in tumours is generally believed to reflect the efficiency of the vascular network. Theoretical studies have suggested that the hypoxic fraction might also be influenced by biological properties of the tumour cells. Quantitative experimental results of cell energy metabolism, hypoxia-induced apoptosis, and radiobiological hypoxia are reported here. Human melanoma multicellular spheroids (BEX-c and WTX-c) were used as tumour models to avoid confounding effects of the vascular network. Radiobiological studies showed that the fractions of hypoxic cells in 1000-μm spheroids were 32 ± 12% (BEX-c) and 2.5 ± 1.1% (WIX-c). The spheroid hypoxic volume fractions (28 ± 6% (BEX-c) and 1.4 ± 7% (WIX-c)), calculated from the rate of oxygen consumption per cell, the cell packing density, and the thickness of the viable rim, were similar to the fractions of radiobiologically hypoxic cells. Large differences between tumours in fraction of hypoxic cells are therefore not necessarily a result of differences in the efficiency of the vascular network. Studies of monolayer cell cultures, performed to identify the biological properties of the BEX-c and WIX-c cells leading to this large difference in fraction of hypoxic cells, gave the following results: (1) WIX-c shelved lower cell surviving fractions after exposure to hypoxia than BEX-c, (2) WIX-c showed higher glucose uptake and lactate release rates than BEX-c both under aerobic and hypoxic conditions, and (3) hypoxia induced apoptosis in WIX-c but not in BEX-c. These observations suggested that the difference between BEX-c and WIX-c spheroids in fraction of hypoxic cells resulted partly from differences in cell energy metabolism and partly from a difference in capacity to retain viability under hypoxic stress. The induction of apoptosis by hypoxia was identified as a phenomenon which has an important influence on the magnitude of the fraction of radiobiologically hypoxic cells in multicellular spheroids.

Original languageEnglish (US)
Pages (from-to)241-249
Number of pages9
JournalInternational journal of radiation biology
Volume70
Issue number3
DOIs
StatePublished - Sep 17 1996

Fingerprint

Cellular Spheroids
Energy Metabolism
Melanoma
Apoptosis
Blood Vessels
Neoplasms
Oxygen Consumption

ASJC Scopus subject areas

  • Radiological and Ultrasound Technology
  • Radiology Nuclear Medicine and imaging

Cite this

Apoptosis, energy metabolism, and fraction of radiobiologically hypoxic cells : A study of human melanoma multicellular spheroids. / Rofstad, E. K.; Eide, K.; Skøyum, R.; Hystad, M. E.; Lyng, H.

In: International journal of radiation biology, Vol. 70, No. 3, 17.09.1996, p. 241-249.

Research output: Contribution to journalArticle

@article{36cb7cffa84748ccaf3b122b291e0f70,
title = "Apoptosis, energy metabolism, and fraction of radiobiologically hypoxic cells: A study of human melanoma multicellular spheroids",
abstract = "The magnitude of the fraction of radiobiologically hypoxic cells in tumours is generally believed to reflect the efficiency of the vascular network. Theoretical studies have suggested that the hypoxic fraction might also be influenced by biological properties of the tumour cells. Quantitative experimental results of cell energy metabolism, hypoxia-induced apoptosis, and radiobiological hypoxia are reported here. Human melanoma multicellular spheroids (BEX-c and WTX-c) were used as tumour models to avoid confounding effects of the vascular network. Radiobiological studies showed that the fractions of hypoxic cells in 1000-μm spheroids were 32 ± 12{\%} (BEX-c) and 2.5 ± 1.1{\%} (WIX-c). The spheroid hypoxic volume fractions (28 ± 6{\%} (BEX-c) and 1.4 ± 7{\%} (WIX-c)), calculated from the rate of oxygen consumption per cell, the cell packing density, and the thickness of the viable rim, were similar to the fractions of radiobiologically hypoxic cells. Large differences between tumours in fraction of hypoxic cells are therefore not necessarily a result of differences in the efficiency of the vascular network. Studies of monolayer cell cultures, performed to identify the biological properties of the BEX-c and WIX-c cells leading to this large difference in fraction of hypoxic cells, gave the following results: (1) WIX-c shelved lower cell surviving fractions after exposure to hypoxia than BEX-c, (2) WIX-c showed higher glucose uptake and lactate release rates than BEX-c both under aerobic and hypoxic conditions, and (3) hypoxia induced apoptosis in WIX-c but not in BEX-c. These observations suggested that the difference between BEX-c and WIX-c spheroids in fraction of hypoxic cells resulted partly from differences in cell energy metabolism and partly from a difference in capacity to retain viability under hypoxic stress. The induction of apoptosis by hypoxia was identified as a phenomenon which has an important influence on the magnitude of the fraction of radiobiologically hypoxic cells in multicellular spheroids.",
author = "Rofstad, {E. K.} and K. Eide and R. Sk{\o}yum and Hystad, {M. E.} and H. Lyng",
year = "1996",
month = "9",
day = "17",
doi = "10.1080/095530096144978",
language = "English (US)",
volume = "70",
pages = "241--249",
journal = "International Journal of Radiation Biology",
issn = "0955-3002",
publisher = "Informa Healthcare",
number = "3",

}

TY - JOUR

T1 - Apoptosis, energy metabolism, and fraction of radiobiologically hypoxic cells

T2 - A study of human melanoma multicellular spheroids

AU - Rofstad, E. K.

AU - Eide, K.

AU - Skøyum, R.

AU - Hystad, M. E.

AU - Lyng, H.

PY - 1996/9/17

Y1 - 1996/9/17

N2 - The magnitude of the fraction of radiobiologically hypoxic cells in tumours is generally believed to reflect the efficiency of the vascular network. Theoretical studies have suggested that the hypoxic fraction might also be influenced by biological properties of the tumour cells. Quantitative experimental results of cell energy metabolism, hypoxia-induced apoptosis, and radiobiological hypoxia are reported here. Human melanoma multicellular spheroids (BEX-c and WTX-c) were used as tumour models to avoid confounding effects of the vascular network. Radiobiological studies showed that the fractions of hypoxic cells in 1000-μm spheroids were 32 ± 12% (BEX-c) and 2.5 ± 1.1% (WIX-c). The spheroid hypoxic volume fractions (28 ± 6% (BEX-c) and 1.4 ± 7% (WIX-c)), calculated from the rate of oxygen consumption per cell, the cell packing density, and the thickness of the viable rim, were similar to the fractions of radiobiologically hypoxic cells. Large differences between tumours in fraction of hypoxic cells are therefore not necessarily a result of differences in the efficiency of the vascular network. Studies of monolayer cell cultures, performed to identify the biological properties of the BEX-c and WIX-c cells leading to this large difference in fraction of hypoxic cells, gave the following results: (1) WIX-c shelved lower cell surviving fractions after exposure to hypoxia than BEX-c, (2) WIX-c showed higher glucose uptake and lactate release rates than BEX-c both under aerobic and hypoxic conditions, and (3) hypoxia induced apoptosis in WIX-c but not in BEX-c. These observations suggested that the difference between BEX-c and WIX-c spheroids in fraction of hypoxic cells resulted partly from differences in cell energy metabolism and partly from a difference in capacity to retain viability under hypoxic stress. The induction of apoptosis by hypoxia was identified as a phenomenon which has an important influence on the magnitude of the fraction of radiobiologically hypoxic cells in multicellular spheroids.

AB - The magnitude of the fraction of radiobiologically hypoxic cells in tumours is generally believed to reflect the efficiency of the vascular network. Theoretical studies have suggested that the hypoxic fraction might also be influenced by biological properties of the tumour cells. Quantitative experimental results of cell energy metabolism, hypoxia-induced apoptosis, and radiobiological hypoxia are reported here. Human melanoma multicellular spheroids (BEX-c and WTX-c) were used as tumour models to avoid confounding effects of the vascular network. Radiobiological studies showed that the fractions of hypoxic cells in 1000-μm spheroids were 32 ± 12% (BEX-c) and 2.5 ± 1.1% (WIX-c). The spheroid hypoxic volume fractions (28 ± 6% (BEX-c) and 1.4 ± 7% (WIX-c)), calculated from the rate of oxygen consumption per cell, the cell packing density, and the thickness of the viable rim, were similar to the fractions of radiobiologically hypoxic cells. Large differences between tumours in fraction of hypoxic cells are therefore not necessarily a result of differences in the efficiency of the vascular network. Studies of monolayer cell cultures, performed to identify the biological properties of the BEX-c and WIX-c cells leading to this large difference in fraction of hypoxic cells, gave the following results: (1) WIX-c shelved lower cell surviving fractions after exposure to hypoxia than BEX-c, (2) WIX-c showed higher glucose uptake and lactate release rates than BEX-c both under aerobic and hypoxic conditions, and (3) hypoxia induced apoptosis in WIX-c but not in BEX-c. These observations suggested that the difference between BEX-c and WIX-c spheroids in fraction of hypoxic cells resulted partly from differences in cell energy metabolism and partly from a difference in capacity to retain viability under hypoxic stress. The induction of apoptosis by hypoxia was identified as a phenomenon which has an important influence on the magnitude of the fraction of radiobiologically hypoxic cells in multicellular spheroids.

UR - http://www.scopus.com/inward/record.url?scp=0029839721&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0029839721&partnerID=8YFLogxK

U2 - 10.1080/095530096144978

DO - 10.1080/095530096144978

M3 - Article

C2 - 8800195

AN - SCOPUS:0029839721

VL - 70

SP - 241

EP - 249

JO - International Journal of Radiation Biology

JF - International Journal of Radiation Biology

SN - 0955-3002

IS - 3

ER -