Effect of antioxidants on hyperoxia-induced chromosomal breakage in Chinese hamster ovary cells: protection by carnosine.
We have studied the effect of various compounds, known as antioxidants, on the level of hyperoxia (80-90% O2)-induced chromosomal aberrations in Chinese hamster ovary cells: ascorbic acid, alpha-tocopherol, carnosine, imidazole-4-acetic acid, glutathione monoethylester, N-acetylcysteine and ethoxyquin. Carnosine (beta-alanyl-histidine) appeared to be the only compound that reduced chromosomal breakage. The effect was also present in cultures post-treated with caffeine (at 2.5 mM, 3 h before harvest), indicating that the apparent protection was not due to selective arrest of chromosomally damaged cells in the G2 phase of the cell cycle. Imidazole-4-acetic acid, a compound structurally very similar to carnosine, had no detectable effect. Ascorbic acid, N-acetylcysteine, glutathione monoethylester and ethoxyquin were found to have a pro-oxidant effect, i.e. they apparently potentiated the clastogenic effect of hyperoxia. Carnosine is the first compound shown to protect against the clastogenicity of normobaric hyperoxia and may thus be a useful tool in elucidating the underlying mechanism.
Institute of Human Genetics, Free University, Amsterdam, The Netherlands.
J J
JJ
Gille
P
P
Pasman
C G
CG
van Berkel
H
H
Joenje
D000111:Acetylcysteine / Q000494:pharmacology; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001205:Ascorbic Acid / Q000494:pharmacology; D002336:Carnosine / Q000494:pharmacology*; D002460:Cell Line; D002869:Chromosome Aberrations; D005015:Ethoxyquin / Q000494:pharmacology; D016195:G2 Phase / Q000187:drug effects; D005978:Glutathione / Q000031:analogs & derivatives / Q000494:pharmacology; D006632:Histamine / Q000031:analogs & derivatives / Q000494:pharmacology; D007093:Imidazoles; D010100:Oxygen / Q000633:toxicity*; D014810:Vitamin E / Q000494:pharmacology
D000975:Antioxidants; D007093:Imidazoles; D014810:Vitamin E; C042431:S-ethyl glutathione; D006632:Histamine; D002336:Carnosine; D005015:Ethoxyquin; D005978:Glutathione; C005954:imidazoleacetic acid; D001205:Ascorbic Acid; D010100:Oxygen; D000111:Acetylcysteine