Health Effects Associated With Pre- and Perinatal Exposure to Arsenic

Abstract

Inorganic arsenic is a well-established human carcinogen, able to induce genetic and epigenetic alterations. More than 200 million people worldwide are exposed to arsenic concentrations in drinking water exceeding the recommended WHO threshold (10μg/l). Additionally, chronic exposure to levels below this threshold is known to result in long-term health effects in humans. The arsenic-related health effects in humans are associated with its biotransformation process, whereby the resulting metabolites can induce molecular damage that accumulates over time. The effects derived from these alterations include genomic instability associated with oxidative damage, alteration of gene expression (including coding and non-coding RNAs), global and localized epigenetic reprogramming, and histone posttranslational modifications. These alterations directly affect molecular pathways involved in the onset and progression of many conditions that can arise even decades after the exposure occurs. Importantly, arsenic metabolites generated during its biotransformation can also pass through the placental barrier, resulting in fetal exposure to this carcinogen at similar levels to those of the mother. As such, more immediate effects of the arsenic-induced molecular damage can be observed as detrimental effects on fetal development, pregnancy, and birth outcomes. In this review, we focus on the genetic and epigenetic damage associated with exposure to low levels of arsenic, particularly those affecting early developmental stages. We also present how these alterations occurring during early life can impact the development of certain diseases in adult life.

In utero arsenic exposure increases DNA damage and gene expression changes in umbilical cord mesenchymal stem cells (UC-MSCs) from newborns as well as in UC-MSC differentiated hepatocytes

“…Accumulated evidence indicates that prenatal and early life arsenic exposure can cause a variety of detrimental health effects during childhood and increase the risk of developing diseases such as bladder, lung, kidney, and liver cancer in adulthood [2] . Our previous findings provide supportive evidence that arsenic exposure in utero was associated with various types of genetic damage in the newborn that may potentially contribute to increased risk of cancer development later in life.…”

“…Cumulative evidence revealed that arsenic is a transplacental carcinogen [1] . Arsenic exposure can cause detrimental health effects, particularly during pregnancy, which is a sensitive period for the developing fetus [2] . In utero arsenic exposure is associated with various types of genetic damage in the newborn such as 8-hydroxydeoxyguanine (8-OHdG), 8-nitroguanine, and micronuclei, which may contribute to the development of a variety of diseases including cancer later in life [3] , [4] .…”

Transporters and Toxicity: Insights From the International Transporter Consortium Workshop 4

“…85 Accumulating evidence strongly suggests that early life exposure to arsenic increases susceptibility to disease. 86 Arsenic transport pathways: Involvement in toxicity and detoxification. Several comprehensive reviews on cellular uptake and efflux pathways for arsenic are available.…”

“…In addition to cancer, chronic arsenic exposure is associated with a myriad of other adverse health effects, including cardiovascular, respiratory, and neurological diseases, skin disorders, and diabetes 85 . Accumulating evidence strongly suggests that early life exposure to arsenic increases susceptibility to disease 86 …”

Arsenic Metabolism, Toxicity and Accumulation in the White Button Mushroom Agaricus bisporus

“…Ranked at the top of the United States Agency for Toxic Substances and Disease Registry (ATSDR)’s priority list of Hazardous Substances, arsenic is a Group 1 (proven) human carcinogen. Chronic exposure is associated with higher chances of a number of diseases [ 1 , 2 , 3 ]. Currently, the maximum contaminant level (MCL) for arsenic in drinking water set by the United States Environmental Protection Agency (EPA) is 10 ppb (parts per billion), a standard accepted by most other countries.…”