Cytotoxicity of diethyldithiocarbamate in human versus rodent cell lines

Diethyldithiocarbamate (DDTC) and other dithiocarbamates are currently receiving attention as potential adjuncts to traditional chemotherapy. In vitro studies with rodent cancer cell lines have consistently shown that DDTC concentrations of 0.1-1.0 micrograms/ml are highly cytotoxic. Paradoxically, however, concentrations of 10-100 micrograms/ml have been significantly less toxic. In the present study, such a 'biphasic' pattern was reproduced when 3 rodent cell lines were exposed for 1 hour to 0.001 to 1000 micrograms DDTC/ml. In contrast, in 7 human cell lines survival decreased steadily with increasing DDTC concentration (in the same dose range) without evidence of a biphasic pattern. These data might have implications for studies in which rodent cell lines are used to model the effects of dithiocarbamates in human tissues.