INDUCTION OF MANGANESE SUPEROXIDE-DISMUTASE GENE-EXPRESSION IN BRONCHOEPITHELIAL CELLS AFTER ROCKWOOL EXPOSURE

Superoxide dismutases play an important protective role in the lung de fense against the pro-oxidative effect of fibrous dusts (e.g. crocidol ite fibers). Particularly crocidolite, but also other asbestos fibers, are known to induce cellular antioxidant defense. Although rockwool, a man-made fiber made from rock, is used widely for insulation purpose s, its effects on the superoxide dismutases in bronchoepithelial cells have not been investigated. Thus, the purpose of this study was to de termine whether human bronchoepithelial cells (BEAS 2B) respond to roc kwool fibers (115-4 experimental rockwool fiber) by induction of MnSOD mRNA and an increase of MnSOD activity levels, The results were compa red with BEAS 2B cells exposed to silica (alpha-quartz: DQ12; SiO2) an d UICC (Union Internationale Contre le Cancer) crocidolite (concentrat ions of all dusts: 0, 2, 5, 10, 25, 50 mu g/cm(2) = 0, 2.4, 6, 12, 30, 60 mu g/ml; 24-h exposure) as control fibers. Scanning electron micro scopy confirmed close dust cell contact under all experimental setting s. Very low MnSOD mRNA baseline levels rose significantly (p < 0.001) in BEAS 2B cells exposed to all three dusts at 2 mu g/cm(2). However, at >25 mu g/cm(2) MnSOD mRNA levels in silica- and crocidolite- but no t in rockwool-exposed cells decreased. Slight (no significance) increa ses of MnSOD activity were observed which decreased at higher dust (>5 mu g/cm(2)) concentrations. These results suggest that: (1) like croc idolite and silica, rockwool accelerates MnSOD gene expression in bron choepithelial cells; (2) an increase of MnSOD mRNA levels is not accom panied by MnSOD activity elevation; (3) in contrast to rockwool, high concentrations (greater than or equal to 25 mu g/cm(2)) of crocidolite and silica reduced MnSOD activity and MnSOD mRNA levels. Because oxid ants (H2O2) and crocidolite fibers were shown to reduce SOD activity, lack of active MnSOD protein may be caused by inactivation on a post-t ranslational level. Furthermore, the decline of MnSOD mRNA and MnSOD a ctivity levels coincides with increasing cytotoxicity. In conclusion, rockwool was demonstrated to induce MnSOD gene expression, perhaps bec ause of its pro-oxidative effect in bronchoepithelial cells. In contra st to crocidolite and silica, rockwool fibers are not cytotoxic in thi s experimental setting.