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 deoxynucleoside analogs may be effective in decreasing the toxicity of ricin. We have therefore examined the effects of 3'-azido-3'-deoxythymidine (AZT) and 2',3'-dideoxycytidine (DDC) in decreasing the cytotoxicity of ricin in J774A.1 macrophage and Chinese hamster ovary (CHO) cells in culture by assessing the release of lactate dehydrogenase (LDH) and aspartate aminotransferase (AST) from the cells, as well as decreased cell viability. The results clearly indicate that DDC provided partial protection 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 systems. When assessing cell viability, DDC almost doubled the viability of 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 exhibits a chemoprotective effect against ricin toxicity in the two cell culture systems employed.
Hassoun
E A
EA
School of Pharmacy and Allied Health Professions, Creighton University, Omaha, NE 68178, USA.
Stohs
S J
SJ
D000818:Animals; D000963:Antimetabolites / Q000494:pharmacology*; D001219:Aspartate Aminotransferases / Q000378:metabolism; D016466:CHO Cells; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D006224:Cricetinae; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects* / Q000201:enzymology; D012276:Ricin / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D016047:Zalcitabine / Q000494:pharmacology*; D015215:Zidovudine / Q000494:pharmacology*
D000963:Antimetabolites; D015215:Zidovudine; D016047:Zalcitabine; D012276:Ricin; D007770:L-Lactate Dehydrogenase; D001219:Aspartate Aminotransferases