ADDING ZN2-CELLS( INDUCES DNA FRAGMENTATION AND CELL CONDENSATION IN CULTURED HUMAN CHANG LIVER)

Zinc (Zn) is a trace element in human cells and regarded as an essenti al nutrient with established deficiency states affecting multiple orga ns in the body. However, it has been reported that Zn uptake is associ ated with some serious harmful effects, such as inhibition of DNA synt hesis and enhanced toxicity from reactive oxygen species. We have prev iously shown that in vivo administration of Zn2+ in C57/6J mice induce s weight loss and massive hair loss where the normal course hair becom es replaced by fine vello hair, simulating the side effects from cance r chemotherapy where oxidative free radical damage is implicated in as sociation with DNA fragmentation and programmed cell death (PCD). Here , in vitro flow cytometric studies on human Chang liver showed Zn2+ ca using cell condensation with DNA fragmentation that occurred in a dose -dependent manner, an effect replicated by micrococcal nuclease digest ion. Specific terminal deoxynucleotidyl transferase- (TdT) mediated la beling of 3'-OH ends of DNA nicks corroborated the flow cytometric pro files of propidium iodide-DNA binding where degradation of both 2 and 4 N genomic DNA resulted in a solitary 1N peak presentation. DNA degra dation concomitant with cell condensation is seen as an established ha llmark of PCD. We further showed that Zn2+ could enhance the generatio n of hydroxyl free radicals (OH .) by the transition metal vanadium. G lutathione, the cell's main reducing agent, underwent corresponding re duction. The results suggested that Zn supplementation could induce fe atures resembling PCD.