Cadmium inhibition of RNA metabolism in murine lymphocytes

Cadmium, as Cd2+, has become an environmental pollutant of significant proportions. We and others have reported that cadmium in in vitro culture can alter several metabolic parameters including the synthesis of RNA. In the present study, a detailed examination of the mechanism of inhibition was undertaken. Cadmium, at 30 microM, decreased cellular uptake of uridine as well as incorporation into RNA up to 60 microM. Above this concentration, uridine incorporation fell to zero while that associated with the lymphocytes remained at a significantly higher value. LPS caused an increase in the fraction of the precursor incorporated into RNA. In the presence of cadmium, the fraction incorporated by non-stimulated cells fell continually while in the stimulated cells, the fraction had increased at 10 microM above which it dropped until at the highest concentration it was as for the unstimulated lymphocytes. It was found that up to 30 microM the ability of LPS to stimulate the lymphocytes in the presence of cadmium was enhanced while above that concentration it decreased so that at 70 microM no stimulation occurred. Cadmium also inhibited the formation of phosphorylated intermediates from uridine with UTP the most affected and the unstimulated lymphocytes the more sensitive. From the study of the intermediate steps it was found that RNA synthesis was directly inhibited and the most sensitive of the several inhibitory points.