Ann. occup. Hyg., Vol. 46, No. suppl_1, pp. 53-57, 2002
© 2002 British Occupational Hygiene Society
Published by Oxford University Press
Role of Iron and Surface Free Radical Activity of Silica in the Induction of Morphological Transformation of Syrian Hamster Embryo Cells
1 Institut National de Recherche et de Sécurité Avenue de Bourgogne, BP no. 27, 54501 Vandoeuvre Cedex, France
2 Dipartimento di Chimica IFM and Interdepartmental Center G. Scansetti for the Study of Asbestos and Other Toxic Particulates, Università di Torino via P. Giuria 9, 10125 Torino, Italy
*Author to whom correspondence should be addressed.
Using various surface modified silica dusts we previously showed that the samples able to generate reactive oxygen species (ROS) induced transformation of Syrian hamster embryo (SHE) cells. The purpose of the present study was to determine in what measure trace iron on the surface of silica particles is involved in the cellular effects, through the formation of ROS. Min-U-Sil 5 quartz (Q) and an amorphous diatomite earth (DE), as well as the same samples pretreated with the Fe chelators ferrozine (fz, 3 mM) and desferrioxamine (dfx, 0.1 mM), were studied for: (i) morphological transformation; and (ii) aberrant mitotic division of SHE cells, which we reported as one of the possible mechanisms of silica-induced cell transformation. In order to determine the nature of the ROS involved in these effects, the antioxidants superoxide dismutase, catalase and mannitol were added to the treated cells. On a per weight basis, DE appeared more cytotoxic and slightly more transforming than Q. The suspensions of Q and DE preincubated in Fe chelators were significantly less transforming and, in particular Q particles, had reduced potency in inducing abnormal mitoses than the untreated samples. Although the amount of Fe mobilized from the silica particles by dfx was greater than that of Fe(II) mobilized by fz, a decrease in transforming potency was largely achieved after pretreatment of particles with fz. In the presence of antioxidants, both the transformation and mitotic aberration frequencies were significantly decreased. The results show that the iron associated with the surface of particles is implicated in the generation of ROS and is partly responsible for the transforming potency of silicas. This study confirms the role of free radical activity in the induction of cell transformation in vitro, suggesting that oxidative stress is one of the mechanisms of silica carcinogenesis.
ROS SHE cell transformation silica surface iron