Role of the Synergistic Interactions of Environmental Pollutants in the Development of Cancer

Abstract

Humanity has altered the planet in multiple ways. Global warming; biodiversity loss; and pollution of land, water, and air are just a few of the myriad human-caused environmental problems (T. A. Burke et al., 2017). However, these problems have also had an impact on humanity itself, including an increase in health problems related to poor environmental and earth conditions (Martin et al., 2009). Environmental pollutants are compounds that have been released into the ecosystem and can pose a serious threat to the well-being of living things. These compounds have been suggested to be responsible for approximately 9 million deaths per year, which correspond to 16% of all deaths worldwide. Indeed, three times more deaths than AIDS, tuberculosis, and malaria combined (Landrigan et al., 2018). Because of the notable adverse effects in different areas of our lives, it has been suggested that pollution research has not received enough attention by international development and global health programs, and that the effects of environmental pollutants on health are underestimated in the calculations of the global burden of disease (Landrigan et al., 2019). Furthermore, joint exposure to various environmental pollutants is almost always overlooked in the regulatory framework and a harmonized and consistent approach to conducting mixture risk assessments and management is lacking (Bopp et al., 2018).

Chemical Toxicants in Water: A GeoHealth Perspective in the Context of Climate Change

“…While many countries monitor drinking water quality, there is a need for a virtually continuous updating of methodologies and safe water quality standards, as advances in water quality quantification and emerging public health concerns lead to the identification of previously unregulated contaminants (Levallois & Villanueva, 2019 ). Furthermore, while focusing on an individual contaminant and its public health impact is beneficial (Almberg et al., 2018 ; Richard et al., 2014 ), there is also a need to shift toward focusing on synergistic interactions between contaminant mixtures (Joseph et al., 2022 ; Lagunas‐Rangel et al., 2022 ; Villanueva & Levallois, 2015 ).…”

DNA damage accumulation and repair defects in FLT3‐ITD acute myeloid leukemia: Implications for clonal evolution and disease progression

“…22 It has been previously 23 ROS are normally present at low and constant levels, playing an important role in cell signaling and homeostasis, but at high concentrations, ROS react rapidly with proteins, lipids, carbohydrates, and nucleic acids, causing irreversible functional alterations or even its complete destruction. 24 FLT3-ITD, by overactivating the STAT5 and PI3K/AKT pathways, maintains and sometimes increases the expression of p22phox and NOX proteins, thus favoring the production of ROS that diffuse into the nucleus and cause DNA damage, especially double-strand breaks and mismatches (Figure 2). 19,20,25,26 Furthermore, the presence of FLT3-ITD at the plasma membrane is required to maintain NOX protein levels and prevent proteosomal degradation of p22phox triggered by GSK3-β signaling.…”

“…For example, intracellular ROS levels are increased in FLT3‐ITD cells compared to wild‐type FLT3 cells, where NOX family NADPH oxidases in the ER and mitochondria are one of the main sources of ROS generation 23 . ROS are normally present at low and constant levels, playing an important role in cell signaling and homeostasis, but at high concentrations, ROS react rapidly with proteins, lipids, carbohydrates, and nucleic acids, causing irreversible functional alterations or even its complete destruction 24 . FLT3‐ITD, by overactivating the STAT5 and PI3K/AKT pathways, maintains and sometimes increases the expression of p22phox and NOX proteins, thus favoring the production of ROS that diffuse into the nucleus and cause DNA damage, especially double‐strand breaks and mismatches (Figure 2).…”

Generation of Endogenous Promoter-Driven Luciferase Reporter System Using CRISPR/Cas9 for Investigating Transcriptional Regulation of the Core Clock Gene BMAL1

“…Circadian rhythm disruption seems to be implicated in several pathologic conditions, including tumorigenesis and the progression of cancer [ 30 , 31 ]. The circadian rhythm affects the progression and chemoresistance of a variety of tumors, including breast cancer, pancreatic cancer, skin cancer, leukemia, and colon cancers, by DNA damage repair and interacting with oncogenes or tumor suppressors [ 32 , 33 , 34 , 35 , 36 , 37 , 38 ]. BMAL1, as the core member of the circadian system, regulates tumor cell apoptosis, cell-cycle progression and DNA damage response, and homoeostasis.…”