Cd2+ responses of cultured human blood cells

Cd2+ cytotoxicity, uptake, and partitioning, and Cd2+-induced metallothioneine synthesis were studied in cultured peripheral human blood cells. Mononuclear cells were found to resist relatively high levels of Cd2+. Few cells were killed below 50 microM Cd2+. Above this value, survival decreased exponentially with dose. The mean LD50 for mononuclear cells cultured in Cd2+ for 40 hr was 100 microM. Polymorphonuclear cells (granulocytes) were found to be more resistant, with a significantly higher threshold and LD50, and a more complex dose response. Most of the Cd2+ incorporated by blood cells was taken up by nucleated cells. Despite their greater resistance, polymorphonuclear cells incorporated more Cd2+ at higher doses (50 to 150 microM) than did mononuclear cells. No Cd2+ was bound to metallothioneine in polymorphonuclear cells following exposure to Cd2+ for even extended periods of time (18 hr) at high doses of 109Cd2+ (25 microM). Instead Cd2+ appeared in a Sephadex G-75 peak of approximately 60,000 Da, as well as in the void peak. No significant amount of preexisting metallothioneine (MT) or metallothioneine mRNA was found in the mononuclear cells. However, MT synthesis was induced rapidly following exposure to Cd2+. [109Cd2+]MT appeared within 1 hr following exposure to 50 microM 109Cd2+, and MT synthesis rates measured from [35S]cysteine incorporation were found to be maximal within 4 hr.