Environmental Toxicants, Epigenetics, and Cancer

Abstract

Tumorigenesis, a complex and multifactorial progressive process of transformation of normal cells into malignant cells, is characterized by the accumulation of multiple cancer-specific heritable phenotypes triggered by the mutational and/or non-mutational (i.e., epigenetic) events. Accumulating evidence suggests that environmental and occupational exposures to natural substances, as well as man-made chemical and physical agents, play a causative role in human cancer. In a broad sense, carcinogenesis may be induced through either genotoxic or non-genotoxic mechanisms; however, both genotoxic and non-genotoxic carcinogens also cause prominent epigenetic changes. This review presents current evidence of the epigenetic alterations induced by various chemical carcinogens, including arsenic, 1,3-butadine, and pharmaceutical and biological agents, and highlights the potential for epigenetic changes to serve as markers for carcinogen exposure and cancer risk assessment.

Epigenetic Changes in Carcinogenesis of Gallbladder

“…However, not much work has been done on epigenetic changes that could be involved in the etiopathogenesis of GBC. This is especially important because epigenetic changes are emerging as a mechanism involved in toxicantinduced malignant transformation for environmental and occupational carcinogens such as arsenicals, cadmium 1,3-butadine, pesticides, pharmaceutical and biological agents [36][37][38][39]. Epigenetic alterations have been reported in cancer of the breast [40,41], lung [42], prostate [43], cervix [44], colorectal [45,46], esophagus [47], stomach [48], head and neck squamous cell carcinoma [49], urinary bladder [50] and osteosarcoma [51].…”

Environment, Epigenetic, and Disease: The Modifiable Trilogy

“…Nickel, chromium and arsenic have also been associated with increased incidence of cancer through changes in both global methylation and at specifi c sets of genes involved in cell cycle regulation, DNA repair, and other crucial cellular functions (Arita and Costa 2009 ;Martinez-Zamudio and Ha 2011 ;Oller et al 1997 ;Pogribny and Rusyn 2013 ;Reichard and Puga 2010 ).…”

The Application of Omics Technologies to the Study of Mammalian Toxicology

“…Identification of different patterns of epigenetic modification may provide insight into the causal mechanisms behind the carcinogenic process [138,139] Historically, epigenetics has been considered from a toxicology perspective to be foremost involved in the process of chemical carcinogenesis [54], primarily because of the association of DNA methylation with cancer during the early 1980s [55]. Indeed, it is for this reason that many research groups have pursued the study of chemical-induced alterations in the epigenome by administering carcinogenic doses of chemicals to animal models, and evaluating changes in the epigenome of the progression to cancer.…”