Mutagenicity and cytotoxicity of N-nitrosothiazolidine-4-carboxylic acid.
N-Nitrosothiazolidine-4-carboxylic acid (NTCA) was prepared by treating L-thioproline with sodium nitrite at pH 2, 37 degrees C. The compound was characterized by mass spectrometry, infrared spectroscopy and 1H-nuclear magnetic resonance spectroscopy. The cytotoxic and mutagenic properties of NTCA were explored by exposing the human cell line HeLa S3 at 37 degrees C to various concentrations (10 microM-10 mM) of the compound for various periods of time (1-36 h) and by monitoring its effects on cell viability, cell growth, intracellular metabolic activities such as DNA, RNA, and protein synthesis and on DNA repair synthesis ('unscheduled' DNA synthesis). NTCA did not affect the cells' viability at any concentration or incubation period but decreased cell growth at the limiting concentration of 10 mM in the growth medium. NTCA had no effect on RNA and protein synthesis, and, similarly, it had no effect on DNA synthesis at concentrations up to 3 mM. Curiously, the stimulation of DNA synthesis by NTCA was seen at 10 mM after 24 h of incubation. NTCA did not initiate 'unscheduled' DNA synthesis (DNA repair). It is concluded that the compound displays very little cytotoxicity and no mutagenicity in the HeLa S3 test system; hence, its presence in humans and in the human food supply is likely to be of little importance as far as its oncogenic properties are concerned.
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Department of Food Science and Technology, University of California, Davis 95616.
Gruenwedel
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D002470:Cell Survival; D003601:Cytotoxicity Tests, Immunologic; D004247:DNA / Q000096:biosynthesis; D006367:HeLa Cells; D009682:Magnetic Resonance Spectroscopy; D009152:Mutagenicity Tests; D009603:Nitroso Compounds / Q000633:toxicity*; D012313:RNA / Q000096:biosynthesis; D013844:Thiazoles / Q000633:toxicity*; D053778:Thiazolidines
D009603:Nitroso Compounds; D013844:Thiazoles; D053778:Thiazolidines; D012313:RNA; C040387:N-nitrosothiazolidine-4-carboxylic acid; D004247:DNA