In vitro effects of thallium on mouse neuroblastoma cells.
To compare the effects of thallium at different cellular levels, cultured mouse neuroblastoma cells (Neuro-2A) were exposed for 24 hr to thallium(I) acetate. The following toxic indicators were assessed in the in vitro test system: cell proliferation by quantification of total protein content of the culture; cytoplasmic membrane integrity to cytosolic lactate dehydrogenase (LDH) leakage; lysosomal hexosaminidase release; lactate dehydrogenase activity; mitochondrial succinate dehydrogenase activity; relative neutral red uptake by lysosomes; lysosomal hexosaminidase sphingolipid degradation activity; acetylcholinesterase activity. The effects of thallium on the various indicators differed. Neural acetylcholinesterase activity was extremely sensitive to T1 inhibition. In contrast, hexosaminidase, an enzyme involved in glycosphingolipid degradation, was stimulated prior to cytoplasmic membrane disruption detected as LDH leakage. Relative neutral red uptake was slightly more sensitive than cell growth inhibition and the reduction in hexosaminidase release suggests an interaction with lysosomes. The low degree of sensitivity of cell proliferation, as judged by the protein content of the cultures, may reflect inhibition of protein degradation. LDH glycolytic activity was severely inhibited, but succinate dehydrogenase activity in the citric acid cycle was increased, probably owing to the mitochondrial accumulation of thallium.
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National Institute of Toxicology, PO Box 863. 41080-Sevilla, Spain.
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