CYTOTOXIC AND TRANSFORMING EFFECTS OF SOME IRON-CONTAINING MINERALS IN SYRIAN-HAMSTER EMBRYO COILS

Four physicochemically characterized iron-containing minerals, one fib rous (a nemalite [brucite]) and three nonfibrous (a biotite [phyllosil icate], a magnetite (Fe3O4), and a goethite [FeOOH alpha]), were studi ed for cytotoxicity and morphological transformation of Syrian hamster embryo (SHE) cells. When colony-forming efficiency was used as a meas ure of cytotoxicity, it appeared that the nemalite was about 1.7-fold more cytotoxic than the biotite and magnetite. However, if the inhibit ory effect on the cell growth was considered the nemalite appeared to be and fold more effective. The analysis of the cell cycle kinetics by flow cytometry revealed a time- and dose-dependent delay in the progr ession of cells through the cell cycle, with the accumulation of cells in S and G(2)-M phases, more particularly in the cultures treated wit h nemalite. While the goethite was neither cytotoxic nor transforming, the other three dusts were, in a dose-dependent manner, efficient in inducing morphological transformation of SHE cells. According to their transforming potency they ranged as follows: nemalite > biotite > mag netite. A 18-fold higher treatment concentration of magnetite than tha t of nemalite was necessary to induce the same transformation frequenc y. The iron chelator desferrioxamine abolished the transforming effect of nemalite. The results suggest that (i) the cytotoxicity and the tr ansformation are induced by some divalent iron-containing minerals and that they are two distinct processes; (ii) there is a varying ability among these dusts to induce cell transformation; and (iii) the bioava ilability of divalent iron leading to formation of reactive iron-oxyge n species could mediate the transforming potency of a mineral. Physico chemical studies correlated to biological effects of many metallic min e dusts are the only approach for understanding their mechanisms of ac tion and their role in occupational pathology.