Limits...
Changes in the ornithine cycle following ionising radiation cause a cytotoxic conditioning of the culture medium of H35 hepatoma cells.

van Rijn J, van den Berg J, Teerlink T, Kruyt FA, Schor DS, Renardel de Lavalette AC, van den Berg TK, Jakobs C, Slotman BJ - Br. J. Cancer (2003)

Bottom Line: A strong decrease in medium arginine is accompanied with parallel increases in ornithine, citrulline and ammonia.Development of cytotoxicity by irradiated cells is completely prevented with the arginase inhibitor L-norvaline, in arginine-deficient medium or when citrulline replaces arginine.These preventive measures result in subtoxic ammonia levels.

View Article: PubMed Central - PubMed

Affiliation: Radiation Oncology, VU Medical Center, Amsterdam, The Netherlands. j.vanrijn@vumc.nl

ABSTRACT
Cultured H35 hepatoma cells release a cytotoxic factor in response to irradiation with X-rays. When the conditioned medium from irradiated cells is given to nonirradiated cells, growth is inhibited and followed by cell death, possibly apoptosis, Analysis of the conditioned medium reveals a dramatic change in the ornithine (urea) cycle components after the irradiation. A strong decrease in medium arginine is accompanied with parallel increases in ornithine, citrulline and ammonia. The high level of ammonia appears to be largely responsible for the observed cytotoxicity. The development of hyperammonia by irradiated cells and the related toxicity depend on the radiation dose and the number of cells seeded thereafter for the medium conditioning. Development of cytotoxicity by irradiated cells is completely prevented with the arginase inhibitor L-norvaline, in arginine-deficient medium or when citrulline replaces arginine. These preventive measures result in subtoxic ammonia levels.

Show MeSH

Related in: MedlinePlus

Composition of the ornithine cycle in the conditioned media from irradiated cells at different cell densities. Conditioned media from irradiated cultures were analysed for ornithine cycle compounds at various times following 8 Gy X-rays for 50 000 (50 k) and 200 000 (200 k) cells. Data are compatible with Figure 3.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC2747531&req=5

fig5: Composition of the ornithine cycle in the conditioned media from irradiated cells at different cell densities. Conditioned media from irradiated cultures were analysed for ornithine cycle compounds at various times following 8 Gy X-rays for 50 000 (50 k) and 200 000 (200 k) cells. Data are compatible with Figure 3.

Mentions: In an attempt to elucidate the nature and identity of the putative cytotoxic factor, CMX was analysed with available routines for medium compounds and various metabolic products. Interestingly, we found remarkable changes in the ornithine or urea cycle in response to increasing doses of X-rays. Whereas arginine rapidly disappears from the medium, ornithine, citrulline and ammonia are produced in large quantities. The effect of cell density on this shift in the ornithine cycle is shown in Figure 5Figure 5


Changes in the ornithine cycle following ionising radiation cause a cytotoxic conditioning of the culture medium of H35 hepatoma cells.

van Rijn J, van den Berg J, Teerlink T, Kruyt FA, Schor DS, Renardel de Lavalette AC, van den Berg TK, Jakobs C, Slotman BJ - Br. J. Cancer (2003)

Composition of the ornithine cycle in the conditioned media from irradiated cells at different cell densities. Conditioned media from irradiated cultures were analysed for ornithine cycle compounds at various times following 8 Gy X-rays for 50 000 (50 k) and 200 000 (200 k) cells. Data are compatible with Figure 3.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2747531&req=5

fig5: Composition of the ornithine cycle in the conditioned media from irradiated cells at different cell densities. Conditioned media from irradiated cultures were analysed for ornithine cycle compounds at various times following 8 Gy X-rays for 50 000 (50 k) and 200 000 (200 k) cells. Data are compatible with Figure 3.
Mentions: In an attempt to elucidate the nature and identity of the putative cytotoxic factor, CMX was analysed with available routines for medium compounds and various metabolic products. Interestingly, we found remarkable changes in the ornithine or urea cycle in response to increasing doses of X-rays. Whereas arginine rapidly disappears from the medium, ornithine, citrulline and ammonia are produced in large quantities. The effect of cell density on this shift in the ornithine cycle is shown in Figure 5Figure 5

Bottom Line: A strong decrease in medium arginine is accompanied with parallel increases in ornithine, citrulline and ammonia.Development of cytotoxicity by irradiated cells is completely prevented with the arginase inhibitor L-norvaline, in arginine-deficient medium or when citrulline replaces arginine.These preventive measures result in subtoxic ammonia levels.

View Article: PubMed Central - PubMed

Affiliation: Radiation Oncology, VU Medical Center, Amsterdam, The Netherlands. j.vanrijn@vumc.nl

ABSTRACT
Cultured H35 hepatoma cells release a cytotoxic factor in response to irradiation with X-rays. When the conditioned medium from irradiated cells is given to nonirradiated cells, growth is inhibited and followed by cell death, possibly apoptosis, Analysis of the conditioned medium reveals a dramatic change in the ornithine (urea) cycle components after the irradiation. A strong decrease in medium arginine is accompanied with parallel increases in ornithine, citrulline and ammonia. The high level of ammonia appears to be largely responsible for the observed cytotoxicity. The development of hyperammonia by irradiated cells and the related toxicity depend on the radiation dose and the number of cells seeded thereafter for the medium conditioning. Development of cytotoxicity by irradiated cells is completely prevented with the arginase inhibitor L-norvaline, in arginine-deficient medium or when citrulline replaces arginine. These preventive measures result in subtoxic ammonia levels.

Show MeSH
Related in: MedlinePlus