Mesothelioma Pathophysiology

The mesothelium consists of a single thin layer of cells forming a cubic epithelium lining the serous cavities of the body including the peritoneumThe pericardium and pleura to form a virtual cavity. The deposition of mineral fibers in the lung may result in their penetration into the visceral pleura from where the fiber can then win the pleural surface, and thus lead to the development of malignant mesothelial plaques. The process leading to the development of peritoneal mesothelioma is not yet known. It was suggested that asbestos fibers from the lung are transported to the abdomen and associated organs via the lymphatic system. In addition, the mineral fibers can be deposited in the intestine after ingestion of sputum contaminated.

It was shown that contamination of the pleura by asbestos or other mineral fibers cause cancer. The long, thin asbestos fibers (blue asbestos, amphibole) Carcinogens are more effective than "feathery fibers" of Chrysotile (or white asbestos). In rats the development of mesothelioma was caused by intra-pleural inoculation of phosphorylated chrysotile fibers. It was suggested that in humans, transport of fibers to the pleura is critical stage in the pathogenesis of mesothelioma. This hypothesis is supported by the observed recruitment of significant numbers of macrophages and other cells immune system to localized lesions caused by asbestos fibers accumulated in the pleural and peritoneal cavities of rats. These lesions continued to attract macrophages in large numbers while the disease progresses, and cellular changes within the lesion resulting in a tumor whose morphology has all the characteristics of malignancy.

The experimental evidence suggests that asbestos acts as a complete carcinogen in the development of mesothelioma occurring in sequential stages of initiation and promotion. The molecular mechanisms underlying malignant transformation of normal mesothelial cells in the presence of asbestos fibers remain unclear despite the demonstration of the oncogenic potential of the substance. However, processing in vitro cells of normal human mesothelial cells to malignant phenotype following exposure to asbestos fibers has not yet been achieved. Generally it is believed that asbestos fibers exert their carcinogenic effect through of direct physical interactions with cells of the mesothelium in conjunction with indirect effects interacting with inflammatory cells such as macrophages. Studies involving intrapleural or intraperitoneal inoculation of different types of asbestos fiber in rats and mice have shown that the long, thin fibers are responsible for a higher incidence of mesothelioma than short fibers and cells phagocytose and store the longest fibers more efficiently than short fibers. Similarly, incubation of Syrian hamster cells with fiberglass with the average length of 9.5μm was caused cellular changes with a speed identical to that of crocidolite. The reduction in the length of these fibers to obtain an approximate size of 2.2 μm reduced the processing capacity of a cellular factor of 10 to 20 were a further reduction to less than 1μm completely suppressed the processing capacity cellular particles of fiberglass.