Immunotoxic effects of mercuric compounds on human lymphocytes and monocytes. II. Alterations in cell viability.
The major goal of this investigation was to examine the cytotoxic properties of both HgCl2 and MeHgCl, in terms of their ability to alter human T-cell and monocyte viability. Following treatment with HgCl2 (0-20 micrograms/ml) or MeHgCl (0-2 micrograms/ml), there was minimal reduction in lymphocyte viability at 1-4 hr. However, after exposure to mercury for 24 hr, cell death was apparent. In comparison, monocytes exhibited significant loss of viability during the early exposure periods. MeHgCl was approximately 5-10 times more potent than HgCl2. Other indicators of cell death were also determined. Measurement of the energy charge ratio indicated profound changes in cellular energy conservation. Electron microscopic analysis of cells treated with mercury revealed early nuclear alterations characterized by hyperchromaticity, nuclear fragmentation and condensation of nucleoplasm. In concert with these nuclear changes, there was destruction of cytoplasmic organelles with loss of membrane integrity. Studies of phospholipid synthesis by mercury treated cells confirmed that there were alterations in membrane structure. Thus, there was a decrease in total phosphatide synthesis by treated cells. Moreover, monocyte phospholipid synthesis appeared to be more sensitive to the presence of mercury then lymphocytes. Finally, both forms of mercury caused a rapid and sustained elevation in the intracellular levels of Ca++. These morphological and biochemical changes are consistent with the notion that mercury initiates cytotoxic changes associated with programmed cell death.
Shenker
B J
BJ
Department of Pathology, University of Pennsylvania School of Dental Medicine, Philadelphia 19104-6002.
Berthold
P
P
Decker
S
S
Mayro
J
J
Rooney
C
C
Vitale
L
L
Shapiro
I M
IM
D000818:Animals; D002118:Calcium / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D004734:Energy Metabolism / Q000187:drug effects; D066298:In Vitro Techniques; D008214:Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008627:Mercuric Chloride / Q000008:administration & dosage / Q000633:toxicity*; D008767:Methylmercury Compounds / Q000008:administration & dosage / Q000633:toxicity*; D008854:Microscopy, Electron; D009000:Monocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D010743:Phospholipids / Q000378:metabolism; D051381:Rats
D008767:Methylmercury Compounds; D010743:Phospholipids; D008627:Mercuric Chloride; C004925:methylmercuric chloride; D002118:Calcium