Epigenetic Effects of Cadmium in Cancer: Focus on Melanoma

Abstract

Cadmium is a highly toxic heavy metal, which has a destroying impact on organs. Exposure to cadmium causes severe health problems to human beings due to its ubiquitous environmental presence and features of the pathologies associated with pro-longed exposure. Cadmium is a well-established carcinogen, although the underlying mechanisms have not been fully under-stood yet. Recently, there has been considerable interest in the impact of this environmental pollutant on the epigenome. Be-cause of the role of epigenetic alterations in regulating gene expression, there is a potential for the integration of cadmium-induced epigenetic alterations as critical elements in the cancer risk assessment process. Here, after a brief review of the ma-jor diseases related to cadmium exposure, we focus our interest on the carcinogenic potential of this heavy metal. Among the several proposed pathogenetic mechanisms, particular attention is given to epigenetic alterations, including changes in DNA methylation, histone modifications and non-coding RNA expression. We review evidence for a link between cadmium-induced epigenetic changes and cell transformation, with special emphasis on melanoma. DNA methylation, with reduced expression of key genes that regulate cell proliferation and apoptosis, has emerged as a possible cadmium-induced epigenetic mechanism in melanoma. A wider comprehension of mechanisms related to this common environmental contaminant would allow a better cancer risk evaluation.

Ten‐year cancer incidence in rescue/recovery workers and civilians exposed to the September 11, 2001 terrorist attacks on the World Trade Center

“…Six weeks after the attacks, exposure to polychlorinated dibenzo‐ p ‐dioxins and dibenzofurans (PCDD/Fs) through soil, and inhalation was up to 2.6 orders of magnitude higher in lower Manhattan than typical background levels measured in mid‐Manhattan and Brooklyn [Rayne, ]. Cadmium in particular, an established carcinogen, has been associated with bladder cancer [Feki‐Tounsi and Hamza‐Chaffai, ], and melanoma [Venza et al, ], but inconsistently with prostate cancer [Waalkes and Rehm, ; Sahmoun et al, ]. In the present study, we observed a significant dose‐response trend for WTC exposure level and urinary bladder cancer among RRW, and for skin melanoma among non‐RRW, but not for other cancers with a statistically significant excess.…”

The In Vitro Anti-Proliferative Interaction of Flavonoid Quercetin and Toxic Metal Cadmium in the 1321N1 Human Astrocytoma Cell Line

“…Additionally, Cd interacts with a variety of DNA repair processes, including base excision repair, nucleotide excision repair, DNA mismatch repair, double-strand break repair and cell-cycle arrest [6]. Moreover, it is demonstrated that Cd induces epigenetic changes through induction of DNA hypomethylation [7], histone modifications and non-coding RNA expression [8]. Quercetin (3,3,4,5,7-pentahydroxyflavone) (QE) belongs to naturally occurring flavonoids and is widely distributed in plants [9].…”

New Frontiers in Melanoma Epigenetics—The More We Know, the More We Don’t Know

“…Moreover, some well-established carcinogens, such as lead and cadmium, have been recently considered as having an impact on the epigenome [172], even though the relation with melanoma was pointed outover 10 years ago [173,174]. Despite the inability to change the gene structure directly, heavy metals, such as cadmium, could interfere with gene expression, probably by inducing epi-mutations, modifying the DNA methylation patterns [172].…”

“…Despite the inability to change the gene structure directly, heavy metals, such as cadmium, could interfere with gene expression, probably by inducing epi-mutations, modifying the DNA methylation patterns [172].…”