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  • 1995-1999  (2)
  • 1965-1969
  • Key words: Gene expression—Crocidolite—Rockwool—Silica—Quartz—Human bronchoepithelial cells—Manganese superoxide dismutase.  (1)
  • PCNA  (1)
Material
Years
  • 1995-1999  (2)
  • 1965-1969
Year
Keywords
  • 1
    ISSN: 1432-1750
    Keywords: Key words: Gene expression—Crocidolite—Rockwool—Silica—Quartz—Human bronchoepithelial cells—Manganese superoxide dismutase.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract. Superoxide dismutases play an important protective role in the lung defense against the pro-oxidative effect of fibrous dusts (e.g. crocidolite 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 purposes, its effects on the superoxide dismutases in bronchoepithelial cells have not been investigated. Thus, the purpose of this study was to determine whether human bronchoepithelial cells (BEAS 2B) respond to rockwool fibers (115-4 experimental rockwool fiber) by induction of MnSOD mRNA and an increase of MnSOD activity levels. The results were compared with BEAS 2B cells exposed to silica (α-quartz: DQ12; SiO2) and UICC (Union Internationale Contre le Cancer) crocidolite (concentrations of all dusts: 0, 2, 5, 10, 25, 50 μg/cm2= 0, 2.4, 6, 12, 30, 60 μg/ml; 24-h exposure) as control fibers. Scanning electron microscopy confirmed close dust cell contact under all experimental settings. Very low MnSOD mRNA baseline levels rose significantly (p 〈 0.001) in BEAS 2B cells exposed to all three dusts at 2 μg/cm2. However, at 〉25 μg/cm2 MnSOD mRNA levels in silica- and crocidolite- but not in rockwool-exposed cells decreased. Slight (no significance) increases of MnSOD activity were observed which decreased at higher dust (〉5 μg/cm2) concentrations. These results suggest that: (1) like crocidolite and silica, rockwool accelerates MnSOD gene expression in bronchoepithelial cells; (2) an increase of MnSOD mRNA levels is not accompanied by MnSOD activity elevation; (3) in contrast to rockwool, high concentrations (≥25 μg/cm2) of crocidolite and silica reduced MnSOD activity and MnSOD mRNA levels. Because oxidants (H2O2) and crocidolite fibers were shown to reduce SOD activity, lack of active MnSOD protein may be caused by inactivation on a post-translational level. Furthermore, the decline of MnSOD mRNA and MnSOD activity levels coincides with increasing cytotoxicity. In conclusion, rockwool was demonstrated to induce MnSOD gene expression, perhaps because of its pro-oxidative effect in bronchoepithelial cells. In contrast to crocidolite and silica, rockwool fibers are not cytotoxic in this experimental setting.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Journal of cancer research and clinical oncology 121 (1995), S. 371-377 
    ISSN: 1432-1335
    Keywords: p53 ; Lung cancer ; Tumor-suppressor gene ; PCNA
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Mutations in thep53 gene are currently the commonest genetic alterations in human malignant tumors, including non-small-cell lung cancer (NSCLC) and small-cell lung cancer (SCLC). Alterations of the protein induced by gene mutations enables the mutant protein to become more stable, resulting in the accumulation of P53 in quantities detectable by immunohistochemistry. Although previous studies document the accumulation of P53 in lung cancer, there is little information regarding the usual frequency of accumulation based on a comprehensive number of lung tumors. A total of 328 paraffin-embedded lung carcinoma specimens were analyzed for P53 accumulation and for the expression of the proliferating-cell nuclear antigen (PCNA) by standard immunohistochemistry. Among 49 SCLC, 35% were positive for p53 and 51% were positive for PCNA. Out of 279 NSCLC, 43% showed a positive P53 immunoreaction and 72% displayed detectable amounts of PCNA. In squamous-cell carcinomas a statistically significant increased accumulation of P53 was found compared to adenocarcinomas (P=0.001). Among the 233 PCNA-positive tumors the relative number of P53-positive specimens was higher compared to the total number of tumors. Since immunohistochemical investigations should contribute to the improvement of the clinical diagnosis and treatment or give information on the prognosis, we conclude from our results that it seems to be legitimate to assess the P53 status exclusively in the specimens positive for PCNA. Immunohistochemical investigations under consideration of the PCNA status yielded good and fast recognition ofp53 mutations leading to intracellular P53 protein accumulation.
    Type of Medium: Electronic Resource
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