Role of Environmental Chemicals, Processed Food Derivatives, and Nutrients in the Induction of Carcinogenesis

Abstract

In recent years it has been hypothesized that cancer stem cells (CSCs) are the actual driving force of tumor formation, highlighting the need to specifically target CSCs to successfully eradicate cancer growth and recurrence. Particularly, the deregulation of physiological signaling pathways controlling stem cell proliferation, self-renewal, differentiation, and metabolism is currently considered as one of the leading determinants of cancer formation. Given their peculiar, slow-dividing phenotype and their ability to respond to multiple microenvironmental stimuli, stem cells appear to be more susceptible to genetic and epigenetic carcinogens, possibly undergoing mutations resulting in tumor formation. In particular, some animal-derived bioactive nutrients and metabolites known to affect the hormonal milieu, and also chemicals derived from food processing and cooking, have been described as possible carcinogenic factors. Here, we review most recent literature in this field, highlighting how some environmental toxicants, some specific nutrients and their secondary products can induce carcinogenesis, possibly impacting stem cells and their niches, thus causing tumor growth.

Repression of Biotin-Related Proteins by Benzo[a]Pyrene-Induced Epigenetic Modifications in Human Bronchial Epithelial Cells

“…Benzo[a]pyrene exposure has been associated with the increased cancer formation through both genetic and epigenetic changes. 21 Consistent with these notions, benzo[a]pyrene diolepoxide (BPDE), the major B[a]P metabolite, has been previously linked to the development of lung cancer in normal 16HBE cells through the formation of BPDE-DNA adducts at mutational hot spots at gene body of tumor suppressor P53. 22 Interestingly, the reduction in BTD expression has also been associated with cancer development, 18,19 and we hypothesized whether there was a link between B[a]P exposure and the change in expression of BTD as well as another key protein in the same biotin homeostasis pathway-HCS.…”

Structure-Dependent Effects of Phthalates on Intercellular and Intracellular Communication in Liver Oval Cells

“…During the chronic liver injury, the proper function of LSPCs is critical and involves their activation, proliferation, and differentiation to mature hepatocytes and bile duct cells [ 20 ]. Thus, the chemically-induced disturbances of LSPC cell regenerative function can disrupt tissue homeostatic mechanisms and contribute to the development and severity of chronic liver toxicities and diseases, including fatty liver diseases, fibrosis, or cirrhosis, and liver cancer [ 21 , 22 , 23 , 24 , 25 , 26 , 27 ]. LSPCs likely proliferate at the early stages of carcinogenesis and might give rise to hepatocytes becoming tumor progenitors [ 17 ].…”

Chemopreventive Agents Attenuate Rapid Inhibition of Gap Junctional Intercellular Communication Induced by Environmental Toxicants

“…Chronic exposure to environmental toxicants inducing the inhibition of GJIC probably represents a very important process involved in the tumor promotion phase of cancer (1, 14), whereas, prevention of GJIC inhibition seems to be crucial for preventing chemically-induced tumor promotion (15, 30) and might be one of the key mechanisms contributing to the potential chemopreventive activity of CPAs. In fact, various plant-derived products and compounds were reported to prevent inhibition of GJIC induced by model tumor promoters (e.g.…”

“…Chemical exposure to environmental and food-borne contaminants has been commonly linked to the etiology of cancers, while consumption of natural or some synthetic compounds has been linked to reduced rates of cancer (1). The underlying cellular properties, known to be critical for cancer development, are DNA alterations by genotoxic mechanisms during the initiation stage of cancer, or alterations of signal transduction pathways and gene expression patterns by non-genotoxic or epigenetic mechanisms, leading primarily to an increase in cell proliferation, inhibition of differentiation, inhibition of apoptosis and inflammatory responses associated with tumor promotion and progression stages of cancer (2, 3).…”