Inhibition by cadmium of thymidine metabolism in concanavalin A-activated murine splenocytes

Add time:09/05/2019    Source:sciencedirect.com

Cadmium has been shown to cause significant inhibition of lymphocyte metabolism, including DNA synthesis, in both in vitro and in vivo studies. In order to understand more clearly the modification of DNA synthesis, this study has examined the metabolism of radiolabelled thymidine in splenocytes exposed to cadmium in vitro. T-lymphocyte-enriched splenocytes were incubated for 48 h with or without Conconavalin A. Cadmium (10 μM) was present during the full period of culture or added at various times after the initiation of the culture. Thymidine metabolism was assessed by examining intracellular metabolite pools, incorporation into DNA, thymidine kinase activity and thymidine membrane transport. Cadmium had little effect on any of these parameters in non-mitogen-stimulated cells. However, in concanavalin A-stimulated cells exposed to cadmium for the full period of culture, the changes in thymidine metabolism normally associated with mitogen activation including increased thymidine incorporation into DNA, expansion of the thymidine di- and triphosphate pools and increased thymidine kinase activity did not occur. Some membrane transport of thymidine did occur but it was less than that of non-cadmium-exposed concanavalin A-stimulated cells. Approximately 90% inhibition of thymidine incorporation into DNA occurs when cadmium is added any time during the first 26 h of culture. When cadmium is present only during the final 6 h of culture, the incorporation is inhibited by approximately 60%. Furthermore, the presence of cadmium during only the last 2 h of culture was shown to inhibit the membrane transport of thymidine, but had no effect on thymidine kinase activity. It is suggested that cadmium interferes with the normal cell cycle progression by concanavalin A binding to the lymphocyte. It is further suggested that since cadmium interferes with the carrier-mediated transport of thymidine, care should be used in interpreting studies involving the use of thymidine incorporation as a measure of DNA synthesis.

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