Short Fibers Induced Only A Small Increase In Labeling Of Bronchiolar Epithelial And Interstitial Ce
One interesting study examing cell proliferation and asbestos related disease is called
, Mesothelial cell proliferation after instillation of long or short asbestos fibers into mouse lung. By I. Y. Adamson, J. Bakowska, and D. H. Bowden - Am J Pathol. 1993 April; 142(4): 12091216. Here is an excerpt: Abstract - The relationship of asbestos deposition in the lung to subsequent cell proliferation at the pleural surface is not clear. The present study examines DNA synthesis by various pulmonary cells, particularly those at the pleura after intratracheal injection of 0.1 mg crocidolite to mice using: 1) long fibers (> 20 mu), which are deposited in bronchiolar regions and induce fibrosis; 2) short fibers (< 1 mu), which reach alveoli but do not induce fibrosis. Mice also received 2 microCi/g tritiated thymidine 1 hour before death at intervals to 16 weeks. Short fibers induced only a small increase in labeling of bronchiolar epithelial and interstitial cells, which subsided by 5 days, when a small increase in labeled mesothelial and subpleural cells was seen. In contrast, long fibers damaged the bronchiolar epithelium and became incorporated into connective tissue. During regeneration, 12% of cells were labeled at 3 days and labeling was greater than controls to 4 weeks. Increased peribronchiolar labeling of fibroblasts and interstitial macrophages was seen around long fibers, and increased DNA synthesis by mesothelial and subpleural cells was found. Up to 2% of mesothelial cells were labeled 1 week after long fibers compared to near zero in controls. No long fibers were found at the pleura. Activation of interstitial macrophages in response to long crocidolite fibers is associated with fibroblast proliferation. It is now suggested that mesothelial cells may also be stimulated by cytokines from activated interstitial macrophages that diffuse across the interstitium, without requiring actual fiber translocation to the pleura.
Another interesting study is called, Incidence of cancer among Finnish patients with asbestos-related pulmonary or pleural fibrosis by Antti Karjalainen, Eero Pukkala, Timo Kauppinen and Timo Partanen - Cancer Causes and Control Volume 10, Number 1, 51-57. Here is an excerpt: Abstract - Objectives: To study the asbestos-associated risk of lung cancer according to the histological type of cancer, the time of and time since diagnosis of asbestosis, the asbestos-associated risk for cancers other than lung cancer or mesothelioma, and the predictive value of asbestos-related pleural abnormalities as regards the risk of cancer. Methods: Finnish patients with asbestosis (n=1,376) or asbestos-related benign pleural disease (n=4,887) notified as an occupational disease since 1964 were followed-up through the Finnish Cancer Registry for cancer in 196795.
Results: Compared with the total cancer incidence in Finland, men with asbestosis had a raised risk of lung cancer (standardized incidence ratio [SIR]=6.7; 95% confidence interval [CI]=5.67.9), mesothelioma (SIR=32, CI=1460) and cancer of the larynx (SIR=4.2, CI=1.49.8). The risk of lung cancer was similarly raised for all histological types of lung cancer (the highest in insulators) and did not change markedly over time of notification or duration of follow-up. Men with benign pleural disease had a raised risk of mesothelioma (SIR=5.5, CI=1.514) and a slightly elevated risk of lung cancer (SIR=1.3, CI=1.01.8). Among women with asbestosis, significant excess was found for lung cancer and mesothelioma. Conclusion: Asbestosis and asbestos-related benign pleural disease seem to possess different predictive values as regards the risk of lung cancer.
Another interesting study is called, Susceptibility of p53-deficient mice to induction of mesothelioma by crocidolite asbestos fibers. By J M Marsella, B L Liu, C A Vaslet, and A B Kane - Department of Pathology and Laboratory Medicine, Brown University School of Medicine, Providence, RI 02912, USA - Environ Health Perspect. 1997 September; 105(Suppl 5): 10691072. Here is an excerpt: Abstract - Exposure of mesothelial cells to asbestos fibers in vitro has been shown to induce DNA damage mediated by oxidants. An early cellular response to DNA damage is increased expression of the p53 protein. This protein induces transcription of genes that activate cell cycle checkpoints or induce apoptosis. A murine mesothelial cell line that spontaneously acquired a point mutation in the p53 gene shows increased sensitivity to DNA damage induced by crocidolite asbestos fibers. It is hypothesized that p53-deficient mice will show increased sensitivity to the genotoxic effects of asbestos and accelerated development of malignant mesotheliomas.
Another interesting study is called, Changes in pulmonary surfactant and phosphatidylcholine metabolism in rats exposed to chrysotile asbestos dust. By T D Tetley, R J Richards, and J L Harwood - Biochem J. 1977 September 15; 166(3): 323329. Here is an excerpt: Abstract - Pulmonary surfactant was isolated from rats that had been exposed to chrysotile asbestos dust for from 3 days to 15 weeks. 2. Asbestos-treated rats showed a progressive increase in amounts of surfactant. After 15 weeks, treated animals contained 4 times as much as non-treated. 3. No significant change was seen in the total protein or total fatty acid composition of surfactant with exposure. 4. The increase in surfactant phosphatidylcholine normally seen on maturation of rat lung was accelerated by exposure of animals to asbestos. 5. An increase in the activity of phosphorylcholine glyceride transferase in lung homogenates and free cell populations was found. 6. Lysosomal phospholipase A was relatively unaffected by dust exposure. 7. It is suggested that the increase in surfactant amounts could be due to an increase in its synthesis without a corresponding alteration in its degradation.
We all owe a debt of gratitude to these fine researchers for their important work. If you found any of these excerpts helpful, please read the studies in their entirety.
by: Mont Wrobleski
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Short Fibers Induced Only A Small Increase In Labeling Of Bronchiolar Epithelial And Interstitial Ce Anaheim