Disruption of Amino Acid Metabolism in Human Myelogenous Leukemic Cell Lines Destined to Die after Contact with Metal Plates

Changes in amino acid metabolism during cell death of human myelogenous leukemic cell lines (HL-1, ML-1, KG-1) induced by contact with gold (Au), silver (Ag) or palladium (Pd) were investigated. All three leukemic cell lines consumed glutamine and serine at the highest rate (amounting to 50%- 58% and 12%-16% of the total amino acid consumption, respectively). HL-60 cell growth was slightly stimulated by contact with any metal plate. Contact with Ag or Pd, but not Au plates occasionally induced cytotoxicity against ML-1 and KG- 1 cells. In such cases, glutamine consumption was inhibited by 88%-90% and consumption of other amino acids completely ceased. This was accompanied by the enhanced production of arginine, glycine and glutamic acid. These data suggest the tight association of the disruption of amino acid metabolism with the cell death induced in human myelogenous leukemic cell lines by contact with metal plates. Dental alloys have been reported to induce allergic reactions in the oral cavity, though infrequently (1), possibly by the stimulated release of metal ions from the alloys (2, 3). The metal ions may be incorporated into the cells, possibly via metal transporter-mediated endocytosis (4, 5). Numerous studies have shown cytotoxic activity and tissue- damaging activity of metal extracts (6-8). As far as we know, however, no detailed study of cytotoxicity induced by direct contact with metals has been reported. We recently developed an assay system to investigate the interaction between metals and cultured cells (9). Using this system, we found that direct contact with a copper (Cu) plate induced non-apoptotic cell death characterized by a smear pattern of DNA fragmentation, minor caspase-3 activation and vacuolization without affecting the cell surface microvilli or mitochondrial integrity in a human promyelocytic leukemic cell line (HL-60) (9). Contact with the Cu plate also induced non-apoptotic cell death accompanied by a rapid decline in glutamine consumption and the enhanced production of glutamic acid and glycine in human gingival fibroblast prepared from periodontal tissues (10). Here, whether the plates of gold (Au), silver (Ag) and palladium (Pd), metals used as constituents in dental alloys, induce cytotoxicity against three human myelogenous leukemic cell lines (HL- 60, ML-1, KG-1), and if so, whether any changes in amino acid metabolism are similar were investigated.