How Asbestos Causes Disease


When inhaled, asbestos fibers in the amphibole group travel down the respiratory passage and embed themselves into the parenchyma of the lung. Because these fibers are not very soluble in the body, they often dig themselves in and can puncture into the deeper tissue.



This penetration of tissue usually starts off locally in the lower lungs and develops into noticeable plaques in the lung pleura. After the deposition of a plaque in the mesothelium, unresolved asbestos fibers can spread further than this primary site. Though the mechanism remains unclear, it is thought that these fibers travel through the lymphatic system (much like many other cancers) to disperse themselves in other areas and associated organs.

Once these asbestos fibers reach their target destinations, the actual conversion of healthy tissue into malignant tissue remains unclear. Several lab experiments and clinical trials that have introduced amphibole fibers to the pleura have yield mixed results. Further research is being done to see if there are other factors necessary for the essential transformation and progression step.

Histologically, the deposition of asbestos seems to mimic a foreign body reaction. Initially, polymorphonuclear neutrophils (PMNs) act as the “first responders” at the scene. These important immune system cells can further trigger response by recruiting other immune system cells to the region. Through a process using chemotaxis, large amounts of macrophages are recruited to the specific areas. These macrophages build up quickly in a matter of days. Over time, the unresolved asbestos lesions can continue to attract and accumulate larger groups of macrophages. Experimental evidence suggests that asbestos acts as a cancer causing agent with the development of mesothelioma occurring sequentially in stages of initiation and promotion. Specific molecular mechanisms underlying the malignant transformation of normal mesothelial cells by asbestos fibers is still not known. In general, asbestos fibers are thought to exert their carcinogenic effects via direct physical interactions with the cells of the mesothelium in a foreign body affect that elicits indirect interaction, recruitment and accumulation of inflammatory cells such as macrophages.

Of curious note, asbestos fibers that have been phagocytosed have shown an interesting interaction with the nucleus. Within the nucleus, there exists the vital information for the well-being of the cell. Specifically, the DNA within the cell seems to be affected by asbestos fibers. Normally, during replication, DNA is tightly wrapped around proteins called histones. On a larger scale, these wrapped DNA strands make up what we call chromosomes. It seems that asbestos fibers can interact with chromosomes and can cause losses, rearrangements and in some cases, unwanted duplications. At that level, small abnormalities can have devastating effects that are often irreparable. Some common gene abnormalities in mesothelioma cell lines include deletion of various tumor suppressor genes.

In a process called transformation used in molecular biology, asbestos has been shown to mediate the entry of foreign DNA into target cells. Successful incorporation of this foreign DNA in key regions and areas can lead to mutations and other changes that specifically promote cancer in a process referred to as oncogenesis. Some possible mechanisms include:

• Inactivation of tumor suppressor genes (eliminating genes that help suppress tumors)
• Activation of oncogenes (genes that can potentially cause cancer)
• Activation of proto-oncogenes due to incorporation of foreign DNA containing a promoter region (transformation)
• Activation of telomerase (an enzyme crucial for the length, stability and lifespan of DNA)
• Prevention of apoptosis (programmed cell death)