Disparate effects of representative dithiocarbamates on selected immunological parameters in vivo and cell survival in vitro in female B6C3F1 mice

Abstract

Recent studies indicate that sodium methyldithiocarbamate is immunotoxic. Major effects of this compound in female B6C3F1 mice include decreased thymus weight, increased spleen weight, and decreased natural killer (NK) cell activity. The effects of other dithiocarbamates on these parameters are not known, and the immunotoxic potential of this important class of compounds is uncertain. In the present study, the effects of sodium methyldithiocarbamate (SMD), sodium diethyldithiocarbamate (DEDTC), and disodium ethylene‐bis(dithiocarbamate)(EBD) on thymus weight, spleen weight, and NK cell activity were compared in female B6C3F1 mice. SMD caused significant loss of thymic weight following oral administration at 200, 225, or 300 mg/kg/d for 7 d and caused significant suppression of splenic NK cell activity at doses of 150, 225, or 300 mg/kg/d for 7 d. In contrast, a dose of 1000 mg/kg/d of DEDTC was required to decrease significantly thymus weight or increase spleen weight, and the only significant change produced by EBD was a slight increase in spleen weight at a dose of 675 mg/kg/d. EBD and DEDTC did not affect NK cell activity at any dose tested. Dithiocarbamates are known to be cytotoxic for a variety of cell types, and it seemed possible that SMD might be more potent in vivo than EBD or DEDTC because it was more cytotoxic than these compounds. However, direct measurement of the cytotoxicity of all three compounds toward splenocytes and thymocytes in vitro demonstrated that SMD and EBD are approximately equally potent (EC₅₀ from 6.1 to 10.5 μM), whereas DEDTC is much more potent (EC₅₀ from 0.13 to 0.15 μM). Of the three compounds examined in this study, only SMD affected thymus weight, spleen weight, and splenic NK cell activity in vivo. Thus, this pattern of immunological effects is not produced by all dithiocarbamates. In addition, the data demonstrate that differences in the potency of SMD, DEDTC, and EBD in vivo do not correlate with their relative cytotoxic potencies in vitro.