CELL-ENHANCED DISSOLUTION OF CARCINOGENIC LEAD CHROMATE PARTICLES - THE ROLE OF INDIVIDUAL DISSOLUTION PRODUCTS IN CLASTOGENESIS

Lead chromate induces chromosomal damage as a result of extracellular dissolution producing solubilized chromium and lead and we show here t hat the dissolution process is greatly accelerated by the presence of cells. We have sought to determine which of these ions is involved in lead chromate-induced clastogenicity. Cell-mediated extracellular diss olution of particulate lead chromate resulted in the accumulation of b oth solubilized chromium acid solubilized lead, reaching concentration s in the extracellular medium of 15 and 1.9 mu M respectively and reac hing concentrations inside the cell of 2700 and 97 mu M respectively. Both the extracellular and intracellular accumulation of chromium was time dependent and both the solubilized lead and chromium increased pr oportionately from a lower dose to a higher dose. Exposing cells to wa ter soluble sodium chromate under conditions which produced similar ti me-dependent intracellular concentrations of chromium also produced a similar amount and spectrum of chromosome damage as lead chromate. In contrast, exposure to lead glutamate resulted in intracellular lead le vels 438-times higher than those produced by lead chromate, but produc ed no chromosome damage. A higher dose of lead glutamate was weakly cl astogenic, but it induced a different spectrum of chromosomal aberrati ons than lead chromate. Pretreatment of cells with vitamin E had no ef fect on the uptake of chromium, but reduced both sodium chromate and l ead chromate-induced clastogenesis by 54-93%. Vitamin E pretreatment d id not affect lead glutamate-induced clastogenesis. The results of thi s study indicate that although lead(II) is weakly clastogenic at high doses, hexavalent chromium is the proximate clastogen in lead chromate -induced clastogenesis. Additionally, this is the first report that pr etreatment of cells with vitamin E can block clastogenesis induced by particulate chromates.