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

J van Rijn*, J van den Berg, T Teerlink, FAE Kruyt, DSM Schor, AC Renardel de Lavalette, TK van den Berg, C Jakobs, BJ Slotman

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

12 Citations (Scopus)
128 Downloads (Pure)

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. (C) 2003 Cancer Research UK.

Original languageEnglish
Pages (from-to)447-454
Number of pages8
JournalBritish Jounal of Cancer
Volume88
Issue number3
DOIs
Publication statusPublished - 10-Feb-2003
Externally publishedYes

Keywords

  • X-rays
  • cytotoxic medium conditioning
  • ornithine cycle
  • hyperammonia
  • IONIZING-RADIATION
  • CLONOGENIC SURVIVAL
  • UNIRRADIATED CELLS
  • HUMAN FIBROBLASTS
  • BYSTANDER
  • METABOLISM
  • DEATH
  • ACID

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