Agency for Toxic Substances and Disease Registry
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Learning Objectives |
Upon completion of this section, you should be able to
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Introduction |
The three main determinants of asbestos toxicity are
The presence of asbestos fibers in the lungs sets off a variety of responses leading to inflammation, cell and tissue damage, which can lead to disease related to fibrosis, or malignancy. The mechanisms by which asbestos causes disease are not fully understood. Currently, there are three hypotheses to account for asbestos’s pathogenicity
Asbestos is genotoxic and carcinogenic. |
Interaction with Cellular Macromolecules |
Because of their surface charge, asbestos fibers can adsorb to cellular macromolecules (proteins, DNA, RNA) and cell surface proteins. Binding of asbestos fibers to these cellular components is believed to induce changes in macromolecular conformation, thereby affecting protein function. Long asbestos fibers have been shown to interfere physically the mitotic spindle and cause chromosomal damage, especially deletions (Broaddus, 2001; ATSDR 2001; National Academy of Sciences, 2006). |
Release of Reactive Oxygen Species |
The presence of asbestos fibers in lung and pleural tissue is also believed to cause the formation and release of reactive oxygen species (ROS). That is, when alveolar macrophages attempt to engulf and digest an asbestos fiber, they release ROS: hydrogen peroxide (H202), and the super oxide radical anion (O2-) (Kamp and Weitzman 1999, 1997). (H202), and the super oxide radical anion (O2-) (Kamp and Weitzman 1999, 1997). Through the Haber-Weiss (or Fenton) reaction, these ROS react with each other to produce hydroxyl radicals, which are even more potent oxidizers. This reaction is believed to be catalyzed by iron present on the surface of the asbestos fibers (Broaddus 2001; ATSDR 2001). |
Other Cell-Mediated Mechanisms |
The presence of asbestos fibers also causes alveolar macrophages, lung cells, and pleural cells to release cellular factors (such as leukotrienes, prostaglandins, TNF-α ) that lead to multiple cellular processes such as
The exact role of all these cellular processes in the formation of fibrosis and malignancy is still being defined (Broaddus 2001; Kamp et al. 2002). |
Primary Sites Affected |
All types of asbestos fibers tend to lodge in the lung at the bronchiolar-alveolar duct bifurcations, and some proceed to the smaller airways and alveolar sacs. From the lung, some fibers can migrate into the pleural space by unknown mechanisms (National Academy of Sciences, 2006). The length of time needed for migration and the number of fibers that successfully migrate may explain why asbestos-induced fibrosis occurs earlier in the lung than the more slowly developing pleural mesothelioma (Broaddus 2001). |
Carcinogenicity |
Asbestos has been designated a known human carcinogen as shown in the following table. All types of asbestos are carcinogenic, but some scientists believe that the amphibole type is more potent in causing mesotheliomas than the serpentine type (chrysotile). However, both types can cause mesotheliomas and are believed to be equally potent in causing lung cancer (ATSDR 2001). |
Agency | Carcinogenicity Classification | Description |
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International Agency for Research on Cancer (IARC) |
1 |
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U.S. Environmental Protection Agency (EPA) |
Group A |
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Key Points |
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Progress Check |