Research of Arsenic Ability to Alter Systems in The Brain

A study conducted by Tyler, C.R., et.al (2014) states that arsenic can alter a multitude of systems in the brain. Of particular interest is HPA axis dysregulation that may underlie several behavioral deficits, particularly related to the hippocampus including alterations in adult neurogensis and Ras-MAPK/ERK signaling. Additionally, arsenic seems to have an impact on cholinergic and monoaminergic signaling, though the mechanisms are not well understood at this point. Rodent studies have provided useful corroboration of the epidemiological evidence suggesting that a number of mechanisms could underlie cognitive deficits and mood disorders observed in human populations. More research focused on the dynamics of epigenetics, particularly on mechanisms of learning and memory and mood, will be important for understanding the impact of arsenic on the brain. Studies on the mechanisms of arsenic-induced toxicity have established that arsenic alters learning and memory in behavioral assays and impacts multiple neurobiological processes including those of neurogenesis and cholinergic, glutamatergic, and monoaminergic signaling pathways. Recent work using animal models has revealed potent alterations in hippocampal function, morphology, and signaling leading to altered cognitive behavior after arsenic exposure.

According to Hong, Y.-S., et.al (2014) Arsenic is the only carcinogen known to cause cancer through respiratory exposure and gastrointestinal exposure. In the 1980s, arsenic was officially recognized as a carcinogenic substance and registered with the International Agency for Research on Cancer (IARC) . After the association between arsenic exposure and carcinogenicity was revealed, studies were conducted in the United States, Taiwan, Bangladesh, India, Argentina, and Chile to further examine this association, and these results supported those of previous reports. Results from animal and epidemiological studies have shown that inorganic arsenic compounds can be categorized as clear carcinogens (group 1) or potential carcinogens (group 2B) such as DMA and MMA, while reobtained and other organ arsenicals have not been categorized as carcinogens (group 3). Several hypotheses regarding the carcinogenicity of inorganic arsenic compounds have been suggested; nevertheless, the biomolecular mechanisms are poorly understood. Nine different hypotheses regarding the toxic mechanism behind arsenic have been suggested, including induced chromosome abnormalities, oxidative stress, altered DNA repair, altered DNA methylation patterns, altered growth factors, enhanced cell proliferation, promotion/progression, suppression of p53, and gene amplification. To date, the IARC has confirmed the association of arsenic exposure with cancers of the skin, lungs, and bladder, while reports on the relationship with the liver, kidney, and prostate cancer remain limited. Key epidemiological evidence regarding the carcinogenicity of arsenic stems from studies from those in Taiwan, Bangladesh, Chile, and Argentina, who consume drinking water containing high concentrations of arsenic (150 µg/L). However, despite the well-established toxicity of arsenic, studies regarding the association between chronic exposure to low concentrations of arsenic and the development of cancer are lacking; further study is needed to support effective public health management.

A study conducted by Lin, H.J., et.al (2013) shows the results of a 20-year retrospective cohort study on liver cancer patients (802 male and 301 female) from 138 communities in Taiwan found a significant increase in liver cancer incidence in both genders at a arsenic concentration above 0.64 mg/L, but no association was found at exposure levels lower than lower 0.64 mg/L. Hopenhayn-Rich et al. observed a significant increase in lung cancer-related deaths with arsenic intake. Moreover, numerous studies have investigated the dose-dependent relationship between arsenic intake and lung cancer incidence, making lung cancer the most well-known cancer associated with arsenic exposure. In a recent study conducted in Taiwan, a high mortality rate and standardized mortality ratio of lung cancer was observed among patients who consumed high-arsenic concentrated drinking water for the past 50 years.

In the general population, measurement of arsenic in the urine has been accepted as the most suitable method. In South Korea, several studies have measured the total arsenic concentration (trivalent, pentavalent, MMA, and DMA) in the urine. In a study by Bae et al. that enrolled 580 Korean adults (242 males and 338 females) 20 years or older, the average the urinary arsenic concentration was 7.10 µg/L (males, 7.63 µg/L; females, 6.75 µg/L). Another study by Eom et al. reported an average concentration of 8.47 µg/L using the same methods. In a high-risk area for arsenic exposure in Bangladesh, the total urine arsenic concentration was 20.77 µg/L on average [58], which is lower than that in China (28.30 µg/L) and Taiwan (20.71 µg/L) [60], but higher than that in Spain (1.14 µg/L). However, these findings cannot be generalized to the South Korean population; thus, further studies regarding arsenic exposure level using representative data in South Korea are needed. When collection data on total arsenic concentration can be difficult to clearly determine the state of arsenic exposure. As such, analysis of the exposure level by separation and quantification of each type of arsenic is needed. In addition, subsequent assessments of arsenic exposure are needed to establish appropriate management policies.