Arsenic toxicity and epimutagenecity: the new LINEage

Abstract

Global methylation pattern regulates the normal functioning of a cell. Research have shown arsenic alter these methylation landscapes within the genome leading to aberrant gene expression and inducts various pathophysiological outcomes. Long interspersed nuclear elements (LINE-1) normally remains inert due to heavy methylation of it's promoters, time and various environmental insults, they lose these methylation signatures and begin retro-transposition that has been associated with genomic instability and cancerous outcomes. Of the various high throughput technologies available to detect global methylation profile, development of LINE-1 methylation index shall provide a cost effect-screening tool to detect epimutagenic events in the wake of toxic exposure in a large number of individuals. In the present review, we tried to discuss the state of research and whether LINE-1 methylation can be considered as a potent epigenetic signature for arsenic toxicity.

Metals and Mechanisms of Carcinogenesis

“…In fact, arsenic has been shown to promote hypermethylation in important tumor suppressor genes such as p53 and p16 (36). Aside from gene-specific DNA, methylation of transposable elements such as long interspersed nuclear elements-1 (LINE-1) and Alu repeats is caused by As exposure (56). LINE-1 are dispersed throughout the genome and have been correlated with multiple human diseases including colon cancer, β-thalassemia, and oculomotor apraxia.…”

“…Since the discovery of arsenic-induced aberrant DNA methylation, new evidence suggests that arsenic-mediated epigenetic changes span from DNA methylation to histone post-translational modifications, as well as changes in miRNA expression (56). Post-translational modification of histone N-terminal tails encompasses a range of events including glycosylation, carbonylation, ubiquitylation, biotinylation, sumoylation, citrullination, ADP-ribosylation, N-formylation, crotonylation, propionylation, butyrylation, proline and aspartic acid isomerization, as well as more common modifications such as methylation, acetylation, and phosphorylation (59).…”

Long INterspersed element‐1 mobility as a sensor of environmental stresses

“…It has been observed that the presence of arsenic leads to a decreased availability of SAM pool within the cell and to a drop in the total methylation index of the genome as well as the histones (Paul and Giri, ); (Bhattacharjee et al ., )). Therefore, it has been suggested that epigenetic alteration can be the most important mechanism causing L1 induction, and that L1 methylation could be considered as a potent epigenetic signature for arsenic toxicity (Paul et al ., ).…”

“…The mechanism underlying arsenic L1 induction is not known; however, numerous studies (Paul et al ., ) found a significant arsenic‐induced L1 hypomethylation. It has been observed that the presence of arsenic leads to a decreased availability of SAM pool within the cell and to a drop in the total methylation index of the genome as well as the histones (Paul and Giri, ); (Bhattacharjee et al ., )).…”

“…Some of the molecular phenomena related to L1‐RTP alteration induced by environmental factors are here briefly summarized. Alteration of methylation level within the L1 promoter CpG island. It was observed in cells subjected to treatment with arsenic (Paul et al ., ), lead (Wright et al ., ), nickel (Brocato and Costa, ), and B(a)P (Teneng et al ., ; Bojang Jr and Ramos, ). It was also observed in rats treated with METH (Moszczynska et al ., ).…”