EFFECT OF METALS AND THEIR ANTAGONISTS ON THE RADICAL INTENSITY AND CYTOTOXICITY OF ASCORBATES

Five heavy metal antagonists were compared for their specificity of ch elating action against copper (CuCl, CuCl2) and iron (FeCl2, FeCl3). E SR spectroscopy showed that both copper and iron significantly enhance d the radical intensity of ascorbate and sodium 5, 6-benzylidene-L-asc orbate (SEA). Equimolar concentrations of dimercaprol efficiently chel ated all these metals, thus significantly reducing their stimulation e ffects. On the other hand the chelating action of penicillamine,(1) et hylenediaminetetraacetic acid and diethylenetriaminepentaacetic acid w as limited to CuCl and CuCl2, whereas deferoxamine mesylate (DFO) was a specific iron chelator. The cytotoxic activity of sodium ascorbate w as augmented by DFO, but diminished by FeCl3. The simultaneous additio n of DFO and FeCl3 counteracted each other thus neutralizing their ind ividual effects The cytotoxic activity of both sodium ascorbate and SE A was significantly enhanced by CuCl2 and this stimulation effect of C uCl2 was effectively chelated by DTPA. The present study demonstrates the specificity of the chelating action of these five antagonists, sug gesting the possible application of these different types of antagonis ts for the prevention of the pathogenic diseases catalyzed by the corr esponding metals.