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Title: Cd/sup 2 +/ responses of cultured human blood cells

Journal Article · · Toxicol. Appl. Pharmacol.; (United States)

Cd/sup 2 +/ cytotoxicity, uptake, and partitioning, and Cd/sup 2 +/-induced metallothioneine synthesis were studied in cultured peripheral human blood cells. Mononuclear cells were found to resist relatively high levels of Cd/sup 2 +/. Few cells were killed below 50 ..mu..M Cd/sup 2 +/. Above this value, survival decreased exponentially with dose. The mean LD50 for mononuclear cells cultured in Cd/sup 2 +/ for 40 hr was 100 ..mu..M. 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 Cd/sup 2 +/ incorporated by blood cells was taken up by nucleated cells. Despite their greater resistance, polymorphonuclear cells incorporated more Cd/sup 2 +/ at higher doses (50 to 150 ..mu..M) than did mononuclear cells. No Cd/sup 2 +/ was bound to metallothioneine in polymorphonuclear cells following exposure to Cd/sup 2 +/ for even extended periods of time (18 hr) at high doses of /sup 109/Cd/sup 2 +/ (25 ..mu..M). Instead Cd/sup 2 +/ 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 Cd/sup 2 +/. (/sup 109/Cd/sup 2 +/)MT appeared within 1 hr following exposure to 50 ..mu..M /sup 109/Cd/sup 2 +/, and MT synthesis rates measured from (/sup 35/S)cysteine incorporation were found to be maximal within 4 hr.

Research Organization:
Los Alamos National Lab., NM
OSTI ID:
6666541
Journal Information:
Toxicol. Appl. Pharmacol.; (United States), Vol. 69
Country of Publication:
United States
Language:
English