Molecular features in arsenic-induced lung tumors

Abstract

Arsenic is a well-known human carcinogen, which potentially affects ~160 million people worldwide via exposure to unsafe levels in drinking water. Lungs are one of the main target organs for arsenic-related carcinogenesis. These tumors exhibit particular features, such as squamous cell-type specificity and high incidence among never smokers. Arsenic-induced malignant transformation is mainly related to the biotransformation process intended for the metabolic clearing of the carcinogen, which results in specific genetic and epigenetic alterations that ultimately affect key pathways in lung carcinogenesis. Based on this, lung tumors induced by arsenic exposure could be considered an additional subtype of lung cancer, especially in the case of never-smokers, where arsenic is a known etiological agent. In this article, we review the current knowledge on the various mechanisms of arsenic carcinogenicity and the specific roles of this metalloid in signaling pathways leading to lung cancer.

Arsenic and human health effects: A review

“…In North America lung cancer, is one of the leading causes of mortality. Arsenic's capability of inducing specific alterations into pathways that regulate tumor formation in lung cells has been elucidated by Hubaux and colleagues (Hubaux et al, 2013) (Figure 14). Increased exposure of arsenic concomitantly increased the susceptibility of lung cancer both in smokers and non-smokers (Järup and Pershagen, 1991).…”

“…Various studies showed the susceptibility of human lungs towards arsenic consumption (Celik et al, 2008;Gibb et al, 2011;Guha Mazumder, 2007) and managed to setup a link between ingestion of iAs through drinking water and human lung cancer development (Ferreccio et al, 2000). Nevertheless, lungs are one of the major targets for tumorigenesis due to arsenic exposure (Hubaux et al, 2013). High mortality rate of patients due to lung cancer has been reported (Hopenhayn-Rich et al, 1998;Lamm et al, 2013;Smith et al, 2012b).…”

Excretion patterns of arsenic and its metabolites in human saliva and urine after ingestion of Chinese seaweed

“…However, recent studies have shown that arsenosugars, the major arsenical constituent of marine algae [9], can be easily metabolised by humans into a multitude of arsenic metabolites, including dimethylarsinic acid (DMA) and its sulphur analogue, thio-DMA, which have been extensively toxicologically characterised [10,11]. Considerable progress has been made in recent years to address arsenic toxicity, including both genetic and epigenetic alteration [12,13]. In spite of these efforts, the putative mechanism underlying arsenic toxicity remains vague given the complicated metabolism of arsenic in the human body, and no effective treatment for arsenicosis exists [3].…”

Circulating Free DNA in Serum and Genomic Alterations of Lung Cancer Patients and High Risk Individuals Exposed to Environmental Pollution

“…In the same period, the Antofagasta region (North of Chile), historically exposed to high levels of drinking water Arsenic (dw-As), showed a mortality rate of 31.6 for both genders, with a rate of 44.2 and 17.4, for men and women, respectively [4][5][6][7][8]. The implementation of earlydetection technologies and prognostic biomarkers are imperative, specifically in cities highly exposed to environmental carcinogens, such as PAHs and Arsenic [9][10][11][12][13]. It is extremely important to have complementary and noninvasive tools, to apply in asymptomatic population, especially to individuals with high risk of LC.…”