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Bioanalytical techniques for detecting biomarkers of response to human asbestos exposure.

Mesaros C, Worth AJ, Snyder NW, Christofidou-Solomidou M, Vachani A, Albelda SM, Blair IA - Bioanalysis (2015)

Bottom Line: Asbestos exposure is known to cause lung cancer and mesothelioma and its health and economic impacts have been well documented.The exceptionally long latency periods of most asbestos-related diseases have hampered preventative and precautionary steps thus far.These studies range from small molecule oxidative stress biomarkers to proteins involved in immune responses.

View Article: PubMed Central - PubMed

Affiliation: 1Penn SRP Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104-6160, USA.

ABSTRACT
Asbestos exposure is known to cause lung cancer and mesothelioma and its health and economic impacts have been well documented. The exceptionally long latency periods of most asbestos-related diseases have hampered preventative and precautionary steps thus far. We aimed to summarize the state of knowledge on biomarkers of response to asbestos exposure. Asbestos is not present in human biological fluids; rather it is inhaled and trapped in lung tissue. Biomarkers of response, which reflect a change in biologic function in response to asbestos exposure, are analyzed. Several classes of molecules have been studied and evaluated for their potential utility as biomarkers of asbestos exposure. These studies range from small molecule oxidative stress biomarkers to proteins involved in immune responses.

No MeSH data available.


Related in: MedlinePlus

Electron microscopy of an ashed lung section after exposure to crocidolite and chrysotileThe crocidolite fibers are at the upper left and the chrysotile fibers are at the lower right.Reprinted with permission from [42] © BMJ Publishing Group Ltd. (1972).
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Figure 4: Electron microscopy of an ashed lung section after exposure to crocidolite and chrysotileThe crocidolite fibers are at the upper left and the chrysotile fibers are at the lower right.Reprinted with permission from [42] © BMJ Publishing Group Ltd. (1972).

Mentions: Since only a small fraction of patients with significant asbestos exposure develop MM, the disease is now thought to progress through a combination of both genetic and environmental factors. For example, the Simian virus 40 T antigen has been detected in many mesotheliomas and has been implicated in the etiology of the disease [41]. Furthermore, some studies have shown that the cyclin-dependent kinase inhibitor 4a (P16INK4a) and ARF tumor suppressor (p14ARF) genes are frequently inactivated in mesothelioma and approximately 50% of MM cases contain missense or nonsense mutations in the neurofibromin type 2 gene. Mice lacking these genes are relatively normal but develop MM at an accelerated rate when exposed to asbestos by intraperitoneal injection. In addition, within the last few years, germ line and sporadic mutations of the tumor suppressor, breast cancer susceptibility (BRCA)-1 associated protein-1 (BAP-1) gene, which expresses a deubiquitinating enzyme, appear to predispose patients to DNA damage after environmental stress [2]. Inhaled asbestos fibers work their way into the lung and ultimately reach the pleural surface (Figure 4) [42] where they are engulfed by tissue phagocytes, primarily macrophages. This process stimulates intracellular ROS production and activates the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway, inducing the release of numerous cytokines (Figure 3). Recent studies suggest that asbestos also activates the nucleotide-binding oligomerization domain-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome thus promoting the release of interleukin (IL)-1β and IL-18 [43]. Furthermore, genetic studies indicate that polymorphisms in genes within the NRLP3 family can both predispose and protect against fibrosis following asbestos exposure. Mice exposed to asbestos exhibit recruitment of activated macrophages to the mesothelium interacting with asbestos fibers. Macrophages are also thought to directly interact with and phagocytose asbestos. It is hypothesized that macrophages and mesothelial cells exposed to asbestos undergo frustrated phagocytosis of elongated fibers; this process is thought to cause chronic production of ROS and cytokines, which contribute to DNA damage and transformation of mesothelial cells [44].


Bioanalytical techniques for detecting biomarkers of response to human asbestos exposure.

Mesaros C, Worth AJ, Snyder NW, Christofidou-Solomidou M, Vachani A, Albelda SM, Blair IA - Bioanalysis (2015)

Electron microscopy of an ashed lung section after exposure to crocidolite and chrysotileThe crocidolite fibers are at the upper left and the chrysotile fibers are at the lower right.Reprinted with permission from [42] © BMJ Publishing Group Ltd. (1972).
© Copyright Policy - open-access - permissions-link
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4487641&req=5

Figure 4: Electron microscopy of an ashed lung section after exposure to crocidolite and chrysotileThe crocidolite fibers are at the upper left and the chrysotile fibers are at the lower right.Reprinted with permission from [42] © BMJ Publishing Group Ltd. (1972).
Mentions: Since only a small fraction of patients with significant asbestos exposure develop MM, the disease is now thought to progress through a combination of both genetic and environmental factors. For example, the Simian virus 40 T antigen has been detected in many mesotheliomas and has been implicated in the etiology of the disease [41]. Furthermore, some studies have shown that the cyclin-dependent kinase inhibitor 4a (P16INK4a) and ARF tumor suppressor (p14ARF) genes are frequently inactivated in mesothelioma and approximately 50% of MM cases contain missense or nonsense mutations in the neurofibromin type 2 gene. Mice lacking these genes are relatively normal but develop MM at an accelerated rate when exposed to asbestos by intraperitoneal injection. In addition, within the last few years, germ line and sporadic mutations of the tumor suppressor, breast cancer susceptibility (BRCA)-1 associated protein-1 (BAP-1) gene, which expresses a deubiquitinating enzyme, appear to predispose patients to DNA damage after environmental stress [2]. Inhaled asbestos fibers work their way into the lung and ultimately reach the pleural surface (Figure 4) [42] where they are engulfed by tissue phagocytes, primarily macrophages. This process stimulates intracellular ROS production and activates the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway, inducing the release of numerous cytokines (Figure 3). Recent studies suggest that asbestos also activates the nucleotide-binding oligomerization domain-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome thus promoting the release of interleukin (IL)-1β and IL-18 [43]. Furthermore, genetic studies indicate that polymorphisms in genes within the NRLP3 family can both predispose and protect against fibrosis following asbestos exposure. Mice exposed to asbestos exhibit recruitment of activated macrophages to the mesothelium interacting with asbestos fibers. Macrophages are also thought to directly interact with and phagocytose asbestos. It is hypothesized that macrophages and mesothelial cells exposed to asbestos undergo frustrated phagocytosis of elongated fibers; this process is thought to cause chronic production of ROS and cytokines, which contribute to DNA damage and transformation of mesothelial cells [44].

Bottom Line: Asbestos exposure is known to cause lung cancer and mesothelioma and its health and economic impacts have been well documented.The exceptionally long latency periods of most asbestos-related diseases have hampered preventative and precautionary steps thus far.These studies range from small molecule oxidative stress biomarkers to proteins involved in immune responses.

View Article: PubMed Central - PubMed

Affiliation: 1Penn SRP Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104-6160, USA.

ABSTRACT
Asbestos exposure is known to cause lung cancer and mesothelioma and its health and economic impacts have been well documented. The exceptionally long latency periods of most asbestos-related diseases have hampered preventative and precautionary steps thus far. We aimed to summarize the state of knowledge on biomarkers of response to asbestos exposure. Asbestos is not present in human biological fluids; rather it is inhaled and trapped in lung tissue. Biomarkers of response, which reflect a change in biologic function in response to asbestos exposure, are analyzed. Several classes of molecules have been studied and evaluated for their potential utility as biomarkers of asbestos exposure. These studies range from small molecule oxidative stress biomarkers to proteins involved in immune responses.

No MeSH data available.


Related in: MedlinePlus