The effect of environmental chemicals on the tumor microenvironment

Abstract

Potentially carcinogenic compounds may cause cancer through direct DNA damage or through indirect cellular or physiological effects. To study possible carcinogens, the fields of endocrinology, genetics, epigenetics, medicine, environmental health, toxicology, pharmacology and oncology must be considered. Disruptive chemicals may also contribute to multiple stages of tumor development through effects on the tumor microenvironment. In turn, the tumor microenvironment consists of a complex interaction among blood vessels that feed the tumor, the extracellular matrix that provides structural and biochemical support, signaling molecules that send messages and soluble factors such as cytokines. The tumor microenvironment also consists of many host cellular effectors including multipotent stromal cells/mesenchymal stem cells, fibroblasts, endothelial cell precursors, antigen-presenting cells, lymphocytes and innate immune cells. Carcinogens can influence the tumor microenvironment through effects on epithelial cells, the most common origin of cancer, as well as on stromal cells, extracellular matrix components and immune cells. Here, we review how environmental exposures can perturb the tumor microenvironment. We suggest a role for disrupting chemicals such as nickel chloride, Bisphenol A, butyltins, methylmercury and paraquat as well as more traditional carcinogens, such as radiation, and pharmaceuticals, such as diabetes medications, in the disruption of the tumor microenvironment. Further studies interrogating the role of chemicals and their mixtures in dose-dependent effects on the tumor microenvironment could have important general mechanistic implications for the etiology and prevention of tumorigenesis.

Airway Exposure to E-Cigarette Vapors Impairs Autophagy and Induces Aggresome Formation

“…aromatic hydrocarbons (8,12,24,25,47,53,54), although recent studies have found that the high-voltage operated e-cigarette generates vapors containing cancer-causing agents such as formaldehyde (29).…”

“…Acute eCV exposure induces accumulation of ubiquitinated proteins and autophagy impairment in murine lungs. (A) C57BL/6 or CD-1 mice were intratracheally (i.t) instilled with carbamazepine (20 mg/kg body weight) or control (0.5% CMC) at time 0 for initial 2 h followed by 3· (2,8, and 21 h) eCV exposure. Broncheoalveolar lavage fluid (BALF) and lungs were harvested for experimental analysis after 24 h as indicated.…”

International regulatory needs for development ofan IATA for non-genotoxic carcinogenic chemical substances

“…Oxidative DNA damage may be critical in carcinogenesis if it results in extensive enough changes to induce gene mutations. However, the induction of oxidative stress may also regulate gene expression either directly through activation of gene transcriptional pathways or indirectly through hypomethylation (Nishida and Kudo, 2013;Casey et al, 2015;Vaccari et al, 2015;Wu and Ni, 2015). Epigenetic mechanisms in relation to regulatory needs are reviewed by Greally and Jacobs (2013) and Marczylo et al (2016), and International Agency for Research on Cancer (IARC) cancer classification by Herceg et al (2013).…”

Health effects of desalinated water: Role of electrolyte disturbance in cancer development

“…diesel exhaust) that could be shown to be 'complete' carcinogens (i.e., substances that could cause cancer on their own). Advances in cancer biology subsequently revealed the limitations of this approach and have let to the multistage and "hallmarks of cancer" framework which recognizes that the cumulative effects of individual (non-carcinogenic) chemicals acting on different pathways, and a variety of related systems, organs, tissues and cells could plausibly conspire to produce tumors and ultimately malignancies (Casey et al, 2015;Hu et al, 2015;Narayanan et al, 2015). We hypothesize that electrolyte disturbance from exposure to demineralized water can mediate the cancer microenvironment in ways that lead to procarcinogenic outcomes.…”