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Chemico-Biological Interactions
Ben-Hur, E., Nuclear Research Center-Negev, P.O. Box 9001, Beer-Sheva, Israel
Prager, A., Nuclear Research Center-Negev, P.O. Box 9001, Beer-Sheva, Israel
Green, M., Nuclear Research Center-Negev, P.O. Box 9001, Beer-Sheva, Israel
Rosenthal, I., Nuclear Research Center-Negev, P.O. Box 9001, Beer-Sheva, Israel
The pH dependence of the phototoxic effects of chloropromazine (CPZ) in Escherichia coli, Salmonella typhimurium and Chinese hamster cells were studied at pH 6-8. All three biological systems displayed higher photosensitization of the drug at lower pH-values. In S. typhimurium the combined action of drug and light also showed mutagenic activity which correlated with toxicity when exposed at pH 7 or 8. When solutions of protein or DNA and CPZ were exposed to near ultraviolet (UV) light, the drug became covalently attached to the macromolecules. This binding was pH dependent but did not correlate with the effects in vivo. It was found however that the permeability of the cells to the drug was enhanced at lower pH-values. It is suggested that the enhanced entrance of CPZ at lower pH-values into the cells facilitated the drug binding to DNA, RNA and proteins within the cells upon light exposure, and that this is the basis for the enhanced phototoxicity and mutagenicity of CPZ. © 1980.
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תנאי שימוש
pH dependence of the phototoxic and photomutagenic effects of chlorpromazine
29
Ben-Hur, E., Nuclear Research Center-Negev, P.O. Box 9001, Beer-Sheva, Israel
Prager, A., Nuclear Research Center-Negev, P.O. Box 9001, Beer-Sheva, Israel
Green, M., Nuclear Research Center-Negev, P.O. Box 9001, Beer-Sheva, Israel
Rosenthal, I., Nuclear Research Center-Negev, P.O. Box 9001, Beer-Sheva, Israel
pH dependence of the phototoxic and photomutagenic effects of chlorpromazine
The pH dependence of the phototoxic effects of chloropromazine (CPZ) in Escherichia coli, Salmonella typhimurium and Chinese hamster cells were studied at pH 6-8. All three biological systems displayed higher photosensitization of the drug at lower pH-values. In S. typhimurium the combined action of drug and light also showed mutagenic activity which correlated with toxicity when exposed at pH 7 or 8. When solutions of protein or DNA and CPZ were exposed to near ultraviolet (UV) light, the drug became covalently attached to the macromolecules. This binding was pH dependent but did not correlate with the effects in vivo. It was found however that the permeability of the cells to the drug was enhanced at lower pH-values. It is suggested that the enhanced entrance of CPZ at lower pH-values into the cells facilitated the drug binding to DNA, RNA and proteins within the cells upon light exposure, and that this is the basis for the enhanced phototoxicity and mutagenicity of CPZ. © 1980.
Scientific Publication
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