TOXIC EFFECTS OF GALLIUM NITRATE ON FRIEND-ERYTHROLEUKEMIA CELLS

Background - Gallium (Ga), is a group III transition metal with proven antitumor activity which shares certain characteristics with iron in that it binds tightly to transferrin and lactoferrin and can be incorp orated into ferritin, Iron is essential for cell growth and viability, while iron deprivation results in inhibition in the synthesis of deox yribonucleotides. Due to the essential role of iron in erythroleukemic cells, we were interested in assessing whether Ga could inhibit growt h of these cells, whether Ga-induced blockade of iron utilization indu ces cell death and, if so, whether this effect could be reversed by ad dition of hemin, Methods - The effects of Ga nitrate on several parame ters of cell viability were examined, Cell cycle status and cellular p orphyrins were analyzed by flow cytometry, The effect of intracellular iron on the growth-inhibitory properties of Ga was studied by loading Friend erythroleukemic cells (FLC) with iron from hemin, Results - Fo llowing treatment of FLC with Ga, flow cytometry revealed cell cycle c hanges and increased fluorescence intensity, Transmission electron mic roscopy and spectral imaging analysis revealed morphological changes a s well as changes in chromatin condensation and cytoplasmic integrity, X-ray microanalysis revealed Na+ and Cl- influx, Hemin was unable to reverse the Ga-induced effects, Conclusions - Addition of Ga to the gr owth medium of cultured FLC results in an intracellular iron deficienc y which cannot be reversed by hemin, and consequently leads to cell de ath.