Internalization, Cytotoxicity, Apoptosis, and Tumor Necrosis Factor-α Expression in Rat Alveolar Macrophages Exposed to Various Dusts Occurring in the Ceramics Industry

Abstract

In 1997 The International Agency for Research on Cancer classified some exposures to crystalline silica as carcinogenic to humans. Such exposures were acknowledged to be very variable, and even in the same monograph it was admitted that coal dust, containing as much as 20% quartz, could not be classified. Clearly there is a need to develop methods for assessing any risks posed by various silica containing dusts in different workplaces. A European collective research project, SILICERAM, was launched with the aim of assessing the toxicity of various dusts in the ceramics industry and improving worker protection. This study examined the effect of particles, namely, DQ12 quartz, China clay, feldspar, and a sample resembling a typical mixture used in the ceramic industry (a “contrived sample” or CS), on NR8383, a rat alveolar macrophage (AM) cell line. Titanium dioxide and aluminum oxide were also used as negative controls. Confocal microscopy observations showed internalization of DQ12 and CS in NR8383. Cell viability decreased dramatically after a 2-h incubation exposure period with DQ12 (−71%). CS was less toxic than DQ12 at 2 h. China clay and feldspar were slightly cytotoxic to NR8383 cells. DQ12 induced apoptosis, with a smaller effect of CS and China clay. TNFα gene expression was analyzed by RT-PCR. DQ12, at a noncytotoxic dose of 10 μ g/cm2, induced a significant expression of TNFα (+2 times increase). In contrast, similar doses of CS and China clay did not produce a significant increase, while TiO2 and Al2O3 displayed no effect. Co-treatment with 10 μ M aluminum lactate significantly reduced the effects of silica-containing particles on cytoxicity, apoptosis, and TNFα expression.