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Biphasic toxicity of diethyldithiocarbamate, a metal chelator, to T lymphocytes and polymorphonuclear granulocytes: Reversal by zinc and copper

Authors
Journal
Biochemical and Biophysical Research Communications
0006-291X
Publisher
Elsevier
Publication Date
Volume
88
Issue
2
Identifiers
DOI: 10.1016/0006-291x(79)92058-8
Disciplines
  • Biology
  • Medicine

Abstract

Abstract A new type of toxicity biphasically dependent on concentration was observed with diethyldithiocarbamate, a metal chelator utilized in medicine. As judged by cell survival and [ 3H]Urd incorporation, diethyldithiocarbamate was maximally toxic to T lymphocytes and polymorphonuclears at 2.5×10 −5 M (first phase) and at higher than 2.5×10 −3 M (second phase), but was not toxic at intermediate concentrations around 2.5×10 −4 M. The response of chelator treated T lymphocytes to phytohemagglutinin was also biphasic. The first toxic phase was partially reversed by 2.5×10 −5 M ZnCl 2, while the second phase was partially reversed by 10 −2 M CuCl 2. This suggests that inhibition of Zn-metalloenzymes in the first phase and of Cu-metalloenzymes in the second may play a crucial role in the mechanism of toxicity. The second toxic phase may be in part due to the observed inhibition of superoxide dismutase rendering the cells susceptible to oxygen toxicity, like obligate anaerobes.

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