The cytotoxic action of diethyldithiocarbamate in vitro. Different inhibition of scheduled and unscheduled DNA synthesis of rat thymic and splenic cells.

Within a concentration range of 1-10 micrograms/ml, an addition of diethyldithiocarbamate (DDC) to splenic and thymic rat lymphocytes (2 X 10(6)-4 X 10(6) cells/ml) resulted in a complete inhibition of scheduled (semiconservative) DNA synthesis. Lower and higher concentrations were less effective. Under the same conditions, a strictly dose-dependent inhibition of unscheduled (excision repair) DNA synthesis, a decrease of the sedimentation rate of nucleoids, as well as changes of the thymidine pool were observed. The results suggest that the cytotoxic action of DDC in vitro may be mediated a) by the chelating properties of the drug with inhibitory effects on a variety of cellular functions, including nucleic acid precursor metabolism, b) by an immediate radiomimetic attack of the SH-group of DDC on the DNA.