POTENTIAL CHEMOPROTECTANT ACTIVITY OF 3'-AZIDO-3'-DEOXYTHYMIDINE (AZT) AND 2',3'-DIDEOXYCYTIDINE (DDC) AGAINST RICIN TOXICITY IN CHINESE-HAMSTER OVARY AND MACROPHAGE J774A.1 CELL-CULTURES

The protein toxin ricin is one of the most toxic substances known. No specific chemoprotective agents are available against ricin or similar protein toxins, Previous investigations have suggested that deoxynucl eoside analogs may be effective in decreasing the toxicity of ricin. W e have therefore examined the effects of 3'-azido-3'-deoxythymidine (A ZT) and 2',3'-dideoxycytidine (DDC) in decreasing the cytotoxicity of ricin in J774A.1 macrophage and Chinese hamster ovary (CHO) cells in c ulture by assessing the release of lactate dehydrogenase (LDH) and asp artate aminotransferase (AST) from the cells, as well as decreased cel l viability, The results clearly indicate that DDC provided partial pr otection against ricin toxicity in both cell culture systems based on the leakage of LDH and AST, Concentration-dependent effects between 10 (-10) and 10(-4) g ml(-1) were produced, Under similar conditions, AZT had no effect on the toxicity of ricin in these two cell culture syst ems, When assessing cell viability, DDC almost doubled the viability o f both CHO and J774A.1 cells at a concentration of 10(-4) g ml(-1) in the presence of ricin. The results demonstrate that DDC but not AZT ex hibits a chemoprotective effect against ricin toxicity in the two cell culture systems employed.