Hydroxyurea: protection of KB cells against the toxic effect of N-methyl-N'-nitro-N-nitrosoguanidine.
This report shows that hydroxyurea (HU) protected KB cells specifically against the toxic effect of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). It appears unlikely that this action was due to stimulation of DNA repair since HU neither protected the cells when added after removal of MNNG, nor shielded them against the toxicity of other DNA damaging agents. Similarly, it seems difficult to account for HU protection by its specific effect as an inhibitor of DNA synthesis, because cell protection was found to be maximal when the proliferative activity of the cultures was minimal, and because much higher doses of HU were required to ensure cell protection than to inhibit DNA synthesis. In fact, the shift of the MNNG dose-response curves in the presence of increasing HU concentrations suggests that HU might interfere with the MNNG-molecule. This was confirmed by our finding that HU enhanced the decomposition rate of MNNG, as did other substances like cysteine or ascorbic acid, which also appeared able to protect the cells against the toxic effect of MNNG.
Aujard
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Institut de Recherches Scientifiques sur le Cancer, Villejuif, France.
Trincal
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D001205:Ascorbic Acid / Q000494:pharmacology; D002273:Carcinogens / Q000037:antagonists & inhibitors / Q000633:toxicity*; D002470:Cell Survival / Q000187:drug effects; D016922:Cellular Senescence / Q000502:physiology; D003545:Cysteine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004347:Drug Interactions; D004355:Drug Stability; D006801:Humans; D006918:Hydroxyurea / Q000494:pharmacology*; D007624:KB Cells; D008769:Methylnitronitrosoguanidine / Q000633:toxicity*; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology*; D012996:Solutions
D002273:Carcinogens; D019384:Nucleic Acid Synthesis Inhibitors; D012996:Solutions; D008769:Methylnitronitrosoguanidine; D003545:Cysteine; D001205:Ascorbic Acid; D006918:Hydroxyurea