Malignant Pleural Mesothelioma And The Asbestos Fiber Burden

Exposure to hazardous asbestos has been shown to cause various malignancies. In fact, over 700,000 people have filed claims for asbestos related injuries in the United States alone. One interesting study that examines cellular abnormalities is called, “Chromosomal abnormalities and their correlations with asbestos exposure and survival in patients with mesothelioma.” By M. Tiainen, L. Tammilehto, J. Rautonen, T. Tuomi, K. Mattson, and S. Knuutila. - Br J Cancer. 1989 October; 60(4): 618–626. Here is an excerpt: “Cytogenetic findings of our 30 previously reported and eight new patients with malignant pleural mesothelioma were summarised and correlated with asbestos fibre burden in lung tissue and survival. Successful cytogenetic analyses were performed on cells obtained from the tumours and/or pleural effusions of 34 of the 38 patients. Clonal chromosomal abnormalities were detected in 25 patients, 19 of them studied before treatment. Nine patients, seven of them studied before treatment, had normal karyotypes and/or non-clonal chromosomal abnormalities. Most of the karyotypic findings in the patients with clonal abnormalities were complex and heterogeneous, and no chromosome aberration specific to mesothelioma could be demonstrated.

The following numerical abnormalities in decreasing order of frequency were preferentially present in karyotypic changes: -22, +7, -1, -3, -9, +11 and -14 (-/+ denoting partial or total loss or gain). Translocations and deletions involving a breakpoint at 1p11-p22 were the most frequent structural aberrations. Statistically significant correlations were found between high content of asbestos fibres in lung tissue and partial or total losses of chromosomes 1 and 4, and a breakpoint at 1p11-p22 (P = 0.0001, P = 0.003, P = 0.009, respectively). The number of copies of chromosome 7 short arms was inversely correlated with survival (P = 0.02). In this study no diagnostic cytogenetic markers of mesothelioma were found, instead the copy number of chromosome 7 short arms turned out to be a possible prognostic factor in malignant mesothelioma.”

Another interesting study is called, “Asbestos causes DNA strand breaks in cultured pulmonary epithelial cells: role of iron-catalyzed free radicals” by D. W. Kamp, V. A. Israbian, S. E. Preusen, C. X. Zhang and S. A. Weitzman - Department of Medicine, Northwestern University Medical School, Chicago, Illinois - Am J Physiol Lung Cell Mol Physiol 268: L471-L480, 1995. Here is an excerpt: “Asbestos causes pulmonary fibrosis and various malignancies by mechanisms that remain uncertain. Reactive oxygen species in part cause asbestos toxicity. However, it is not known whether asbestos-induced free radical production causes alveolar epithelial cell (AEC) cytotoxicity by inducing DNA strand breaks (DNA-SB). We tested the hypothesis that asbestos-induced AEC injury in vitro is due to iron-catalyzed free radical generation, which in turn causes DNA-SB. We found that amosite asbestos damages cultured human pulmonary epithelial-like cells (WI-26 cells) as assessed by 51Cr release and that an iron chelator, phytic acid (500 microM), attenuates these effects.

A role for iron causing these effects was supported by the observation that ferric chloride-treated phytic acid did not diminish WI-26 cell injury. Production of hydroxyl radical-like species (.OH) was assessed based upon the .OH-dependent formation of formaldehyde (HCHO) in the presence of dimethyl sulfoxide. A variety of mineral dusts induced significant levels of .OH formation (nmol HCHO at 30 min: carbonyl iron, 85 +/- 21; amosite asbestos, 14 +/- 2; chrysotile asbestos, 7 +/- 1; titanium dioxide, 2.5 +/- 0.5). Phytic acid significantly diminished the asbestos-induced .OH production. DNA damage to AEC was assessed by the alkaline unwinding, ethidium bromide fluorometric technique. Hydrogen peroxide caused dose-dependent DNA-SB in WI-26 cells after a 30-min exposure period [50% effective dose (ED50): 5 microM] that was similar to other cell lines. Amosite asbestos induced dose-dependent DNA-SB in WI-26, A549, and primary isolated rat alveolar type II cells maintained in culture for 7-10 days (alveolar type I-like). Lower doses of amosite (0.5-5 micrograms/ml or 0.25-2.5 micrograms/cm2) caused significant WI-26 cell DNA-SB after prolonged exposure periods (> or = 2 days). Phytic acid ameliorated DNA damage in all three cultured AEC. There was a direct correlation between mineral dust-induced .OH production at 30 min and DNA-SB in WI-26 cells at 4 h (P < 0.0005). These data suggest that mineral dusts can be directly genotoxic to relevant target cells of asbestos, AEC. Furthermore, these results provide additional support for the premise that iron-catalyzed free radicals mediate asbestos-induced pulmonary toxicity.”

If you found any of these excerpts interesting, please read the studies in their entirety. We all owe a great debt to these researchers for their important work.

By: Mont Wrobleski

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Monty Wrobleski is the author of this article on Texas Mesothelioma Attorney Texas Mesothelioma Lawyer