**3.3 Carcinogenic potential of other fibers**

While the oncogenic effects of asbestos have been extensively established, recent evidence indicates that non-asbestos fibers, both natural and synthetic in nature can also cause thoracic cancers. Non-asbestos mineral (natural) fibers include erionite and fluoro-edenite, among others. Erionite is a naturally occurring fibrous mineral that shares some physical properties with asbestos, although it is less widespread. In fact, it has been shown that erionite is a more potent carcinogen in causing malignant mesothelioma [87, 88]. Erionite activates the NLR family pyrin domain containing 3 (*NLRP3, NALP3*) inflammasome, inducing the transcription and production of cytokines critical to cancer initiation [89]. On the other hand, Fluoro-edenite (originating from volcanic activity) can induce ROS that result in DNA damage and increase in lactic dehydrogenase release (a damage and toxicity marker) in human lung adenocarcinoma (A549) and monocyte-macrophage (J774) cell lines [90].

**79**

**4. Radon**

decay (**Figure 3**) [98].

progeny of radon [99].

*Oncogenetics of Lung Cancer Induced by Environmental Carcinogens*

**4.1 Physiological and molecular impact of exposure**

Synthetic graphene-based fibers are widely used in several industries. They have also been explored as a drug delivery system for cancer treatments. Physical similarities to asbestos, particularly its high length-to-width ratio, have raised some concerns about the potential carcinogenicity effects of these fibers [91]. Exposure to carbon nanotubules has been shown to induce oncogenic pathways, such as TGF-β and Akt/GSK-3β, resulting in activation of the SNAIL-1 signaling pathway and epithelial-mesenchymal transition [92]. Additionally, carbon nanotubules can generate ROS, activating MAPKs, AP-1, NF-κB, and Akt in normal and malignant human mesothelial cells [93]. Other genetic alterations, including micronuclei formation, disruption of mitotic spindles, and polyploidy have also been observed in response to carbon nanotubule exposure [94–96]. Moreover, it has been shown that exposure to carbon nanotubules can induce specific methylation changes at the promoter regions several genes, including *DNMT1*, *ATM*, *SKI*, and *HDAC4*, while they seem to have only a marginal effect on miRNA expression [97]. Thus, the oncogenetic factors of natural and synthetic fibers, while similar in morphology, are distinct entities that may collectively culminate in tumor development.

Radon is the second most common cause of lung cancer in many countries; however, the intricacies of its mechanism of action remain underappreciated. The genotoxicity of radon is largely the result of alpha particle emission during its spontaneous decay into short-lived radioactive progeny (218Po and 214Po) and comparably long-lived radioactive 210Pb, which also induces cellular damage through alpha

Alpha decay is the emission of a 4 atomic mass unit helium ion (two protons and two neutrons), which can liberate electrons from water molecules and result in the generation of several types of ROS [15]. Much like the mechanisms of arsenic and asbestos toxicity, ROS generated as a consequence of radon exposure can lead to widespread molecular aberrations, especially base oxidation (leading to mismatches and mutagenesis), DNA strand breaks, chromosomal aberrations, and deletions. For example, chromatid deletions in blood lymphocytes may be a result of radon exposure, which may in part explain the associations between radon exposure and blood malignancies [8]. These events may occur at levels well below those currently deemed safe in many countries, exemplified by the observation of chromosomal abnormalities in lymphocytes at very low doses of polonium-214, a radioactive

Beyond the molecular events resulting from ROS generation, alpha radiation from radon exposure can induce bystander responses in cells that have not been directly affected by alpha particles [100]. The bystander effect of radiation exposure can occur through the release of signals from nearby irradiated cells, generating a physiological response in non-irradiated cells, even at relatively low doses of radiation [101]. The effect requires direct contact between adjacent cells, such as through gap junctions, as well as compounds in the surrounding medium, including cytokines [102]. One of these compounds, nitric oxide (NO), has been shown to be an important factor for the cell-killing effects of the bystander response, largely through the direct interaction with and damage of DNA [103]. Moreover, NO byproducts such as dinitrogen trioxide (N2O3) can promote nitrosation of other amines, such as those of DNA bases, leading to cross-linking and DNA alkylation [102]. Another compound that may be relevant to the bystander effect of cellular

*DOI: http://dx.doi.org/10.5772/intechopen.81064*

*Oncogenetics of Lung Cancer Induced by Environmental Carcinogens DOI: http://dx.doi.org/10.5772/intechopen.81064*

Synthetic graphene-based fibers are widely used in several industries. They have also been explored as a drug delivery system for cancer treatments. Physical similarities to asbestos, particularly its high length-to-width ratio, have raised some concerns about the potential carcinogenicity effects of these fibers [91]. Exposure to carbon nanotubules has been shown to induce oncogenic pathways, such as TGF-β and Akt/GSK-3β, resulting in activation of the SNAIL-1 signaling pathway and epithelial-mesenchymal transition [92]. Additionally, carbon nanotubules can generate ROS, activating MAPKs, AP-1, NF-κB, and Akt in normal and malignant human mesothelial cells [93]. Other genetic alterations, including micronuclei formation, disruption of mitotic spindles, and polyploidy have also been observed in response to carbon nanotubule exposure [94–96]. Moreover, it has been shown that exposure to carbon nanotubules can induce specific methylation changes at the promoter regions several genes, including *DNMT1*, *ATM*, *SKI*, and *HDAC4*, while they seem to have only a marginal effect on miRNA expression [97]. Thus, the oncogenetic factors of natural and synthetic fibers, while similar in morphology, are distinct entities that may collectively culminate in tumor development.
