Cytotoxic and transforming effects of some iron-containing minerals in Syrian hamster embryo cells.
Four physicochemically characterized iron-containing minerals, one fibrous (a nemalite [brucite]) and three nonfibrous (a biotite [phyllosilicate], a magnetite (Fe3O4), and a goethite [FeOOH alpha]), were studied for cytotoxicity and morphological transformation of Syrian hamster embryo (SHE) cells. When colony-forming efficiency was used as a measure of cytotoxicity, it appeared that the nemalite was about 1.7-fold more cytotoxic than the biotite and magnetite. However, if the inhibitory effect on the cell growth was considered the nemalite appeared to be 8-fold more effective. The analysis of the cell cycle kinetics by flow cytometry revealed a time- and dose-dependent delay in the progression of cells through the cell cycle, with the accumulation of cells in S and G2-M phases, more particularly in the cultures treated with 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 > magnetite. A 18-fold higher treatment concentration of magnetite than that of nemalite was necessary to induce the same transformation frequency. The iron chelator desferrioxamine abolished the transforming effect of nemalite. The results suggest that (i) the cytotoxicity and the transformation 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 bioavailability of divalent iron leading to formation of reactive iron-oxygen species could mediate the transforming potency of a mineral. Physicochemical studies correlated to biological effects of many metallic mine dusts are the only approach for understanding their mechanisms of action and their role in occupational pathology.
Elias
Z
Z
Department of Experimental Industrial Toxicology, National Institute of Research and Security (INRS), Vandoeuvre, France.
Poirot
O
O
Schneider
O
O
Marande
A M
AM
Danière
M C
MC
Terzetti
F
F
Pezerat
H
H
Fournier
J
J
Zalma
R
R
D000538:Aluminum Silicates / Q000633:toxicity*; D000818:Animals; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000139:chemically induced*; D002478:Cells, Cultured; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D052203:Ferrosoferric Oxide; D005296:Ferrous Compounds / Q000633:toxicity*; D007501:Iron / Q000633:toxicity*; D058085:Iron Compounds / Q000633:toxicity*; D008903:Minerals; D010087:Oxides / Q000633:toxicity*
D000538:Aluminum Silicates; D005296:Ferrous Compounds; D058085:Iron Compounds; D008903:Minerals; D010087:Oxides; C047410:biotite; C094886:goethite; D007501:Iron; D052203:Ferrosoferric Oxide