Increased cellular hypoxia and reduced proliferation of both normal and leukaemic cells during progression of acute myeloid leukaemia in rats

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Increased cellular hypoxia and reduced proliferation of both normal and leukaemic cells during progression of acute myeloid leukaemia in rats. / Jensen, P O; Mortensen, B T; Hodgkiss, R J; Iversen, P O; Christensen, I J; Helledie, N; Larsen, J K.

In: Cell Proliferation, Vol. 33, No. 6, 12.2000, p. 381-95.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Jensen, PO, Mortensen, BT, Hodgkiss, RJ, Iversen, PO, Christensen, IJ, Helledie, N & Larsen, JK 2000, 'Increased cellular hypoxia and reduced proliferation of both normal and leukaemic cells during progression of acute myeloid leukaemia in rats', Cell Proliferation, vol. 33, no. 6, pp. 381-95.

APA

Jensen, P. O., Mortensen, B. T., Hodgkiss, R. J., Iversen, P. O., Christensen, I. J., Helledie, N., & Larsen, J. K. (2000). Increased cellular hypoxia and reduced proliferation of both normal and leukaemic cells during progression of acute myeloid leukaemia in rats. Cell Proliferation, 33(6), 381-95.

Vancouver

Jensen PO, Mortensen BT, Hodgkiss RJ, Iversen PO, Christensen IJ, Helledie N et al. Increased cellular hypoxia and reduced proliferation of both normal and leukaemic cells during progression of acute myeloid leukaemia in rats. Cell Proliferation. 2000 Dec;33(6):381-95.

Author

Jensen, P O ; Mortensen, B T ; Hodgkiss, R J ; Iversen, P O ; Christensen, I J ; Helledie, N ; Larsen, J K. / Increased cellular hypoxia and reduced proliferation of both normal and leukaemic cells during progression of acute myeloid leukaemia in rats. In: Cell Proliferation. 2000 ; Vol. 33, No. 6. pp. 381-95.

Bibtex

@article{03c9832a958244dbba7cd73f16eacd57,
title = "Increased cellular hypoxia and reduced proliferation of both normal and leukaemic cells during progression of acute myeloid leukaemia in rats",
abstract = "The microenvironmental changes in the bone marrow, spleen and liver during progression of the transplantable promyelocytic leukaemia in the Brown Norwegian rat (BNML) have been studied. We used flow cytometry to estimate cellular hypoxia and proliferation based on in vivo pulse-labelling with a mixture of 2-nitroimidazole linked to theophylline (NITP) and bromodeoxyuridine (BrdUrd). The leukaemic cells were identified with the RM124 antibody. In rats inoculated with leukaemic cells the fraction of RM124+ cells was significantly increased from day 20 onwards in the spleen and from day 27 in the bone marrow and liver, reaching a level of 65-87% in these organs at day 32. At day 32, the NITP+ fraction of RM124+ cells had increased significantly in the bone marrow and spleen to 88% and 90%, respectively. The corresponding fractions of NITP+ normal cells reached 63% and 65%, respectively. From day 13 to day 32, the DNA-synthesizing (BrdUrd+) fraction of RM124+ cells in the bone marrow decreased significantly from 52% to 25%, and of normal cells from about 20% to 6%. In the bone marrow and spleen at day 27 and 32, the S-phase and G2/M-phase fractions according to DNA content were higher for the NITP+ than for the NITP- cells. This could partly be explained by an impaired cell cycle progression due to hypoxia. Nevertheless, we found indications of leukaemic cells that were simultaneously labelled with NITP and BrdUrd, in the bone marrow and spleen. These latter findings suggest that in contrast to normal cells some of the leukaemic cells can proliferate even during hypoxia, and this subpopulation may consequently renew and expand the leukaemic cell load.",
keywords = "Acute Disease, Animals, Cell Division, Cell Hypoxia, Disease Models, Animal, Disease Progression, Leukemia, Myeloid, Oxygen, Rats, Rats, Inbred BN, Tumor Cells, Cultured, Journal Article, Research Support, Non-U.S. Gov't",
author = "Jensen, {P O} and Mortensen, {B T} and Hodgkiss, {R J} and Iversen, {P O} and Christensen, {I J} and N Helledie and Larsen, {J K}",
year = "2000",
month = dec,
language = "English",
volume = "33",
pages = "381--95",
journal = "Cell Proliferation",
issn = "0960-7722",
publisher = "Wiley-Blackwell",
number = "6",

}

RIS

TY - JOUR

T1 - Increased cellular hypoxia and reduced proliferation of both normal and leukaemic cells during progression of acute myeloid leukaemia in rats

AU - Jensen, P O

AU - Mortensen, B T

AU - Hodgkiss, R J

AU - Iversen, P O

AU - Christensen, I J

AU - Helledie, N

AU - Larsen, J K

PY - 2000/12

Y1 - 2000/12

N2 - The microenvironmental changes in the bone marrow, spleen and liver during progression of the transplantable promyelocytic leukaemia in the Brown Norwegian rat (BNML) have been studied. We used flow cytometry to estimate cellular hypoxia and proliferation based on in vivo pulse-labelling with a mixture of 2-nitroimidazole linked to theophylline (NITP) and bromodeoxyuridine (BrdUrd). The leukaemic cells were identified with the RM124 antibody. In rats inoculated with leukaemic cells the fraction of RM124+ cells was significantly increased from day 20 onwards in the spleen and from day 27 in the bone marrow and liver, reaching a level of 65-87% in these organs at day 32. At day 32, the NITP+ fraction of RM124+ cells had increased significantly in the bone marrow and spleen to 88% and 90%, respectively. The corresponding fractions of NITP+ normal cells reached 63% and 65%, respectively. From day 13 to day 32, the DNA-synthesizing (BrdUrd+) fraction of RM124+ cells in the bone marrow decreased significantly from 52% to 25%, and of normal cells from about 20% to 6%. In the bone marrow and spleen at day 27 and 32, the S-phase and G2/M-phase fractions according to DNA content were higher for the NITP+ than for the NITP- cells. This could partly be explained by an impaired cell cycle progression due to hypoxia. Nevertheless, we found indications of leukaemic cells that were simultaneously labelled with NITP and BrdUrd, in the bone marrow and spleen. These latter findings suggest that in contrast to normal cells some of the leukaemic cells can proliferate even during hypoxia, and this subpopulation may consequently renew and expand the leukaemic cell load.

AB - The microenvironmental changes in the bone marrow, spleen and liver during progression of the transplantable promyelocytic leukaemia in the Brown Norwegian rat (BNML) have been studied. We used flow cytometry to estimate cellular hypoxia and proliferation based on in vivo pulse-labelling with a mixture of 2-nitroimidazole linked to theophylline (NITP) and bromodeoxyuridine (BrdUrd). The leukaemic cells were identified with the RM124 antibody. In rats inoculated with leukaemic cells the fraction of RM124+ cells was significantly increased from day 20 onwards in the spleen and from day 27 in the bone marrow and liver, reaching a level of 65-87% in these organs at day 32. At day 32, the NITP+ fraction of RM124+ cells had increased significantly in the bone marrow and spleen to 88% and 90%, respectively. The corresponding fractions of NITP+ normal cells reached 63% and 65%, respectively. From day 13 to day 32, the DNA-synthesizing (BrdUrd+) fraction of RM124+ cells in the bone marrow decreased significantly from 52% to 25%, and of normal cells from about 20% to 6%. In the bone marrow and spleen at day 27 and 32, the S-phase and G2/M-phase fractions according to DNA content were higher for the NITP+ than for the NITP- cells. This could partly be explained by an impaired cell cycle progression due to hypoxia. Nevertheless, we found indications of leukaemic cells that were simultaneously labelled with NITP and BrdUrd, in the bone marrow and spleen. These latter findings suggest that in contrast to normal cells some of the leukaemic cells can proliferate even during hypoxia, and this subpopulation may consequently renew and expand the leukaemic cell load.

KW - Acute Disease

KW - Animals

KW - Cell Division

KW - Cell Hypoxia

KW - Disease Models, Animal

KW - Disease Progression

KW - Leukemia, Myeloid

KW - Oxygen

KW - Rats

KW - Rats, Inbred BN

KW - Tumor Cells, Cultured

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

M3 - Journal article

C2 - 11101010

VL - 33

SP - 381

EP - 395

JO - Cell Proliferation

JF - Cell Proliferation

SN - 0960-7722

IS - 6

ER -

ID: 181873711