CYANIDE-INDUCED DNA FRAGMENTATION IN MAMMALIAN-CELL CULTURES

Cyanide is a mitochondrial poison and its toxicity is mediated through histotoxic hypoxia. Although cyanide is regarded as a neurotoxin, its other toxic manifestations are also well documented. Cyanide triggers all those events which can lead to DNA damage, but its genotoxic pote ntial has not been established yet. The present investigation addresse s the DNA damage induced by cyanide in rat thymocytes in vitro. Cell v iability (eosin Y exclusion and LDH leakage) along with DNA strand bre aks were measured in thymocytes exposed to 1.25-10 mM KCN for various time intervals. Cleavage into oligonucleosomal fragments of extracted DNA from cyanide treated thymocytes were visualized on gel electrophor esis. Cyanide produced both time and dose dependent DNA fragmentation accompanied by cytotoxicity. The DNA damage was sensitive to elevated levels of extracellular Ca2+ and was minimal in Ca2+ free medium. The DNA fragmentation was attenuated by Zn2+ (modulator of Ca2+/Mg2+-depen dent endonuclease), N-acetylcysteine (free radical scavenger) and dilt iazem (Ca2+ channel blocker). Cyanide induced DNA damage was further o bserved in baby hamster kidney cells (BHK-21), where unlike thymocytes , internucleosomal DNA fragmentation was not observed. Thymocytes were more sensitive to cyanide as compared to BHK-21 cells. (C) 1997 Elsev ier Science Ireland Ltd.