Genotoxicity of Mercury and Its Derivatives Demonstrated In Vitro and In Vivo in Human Populations Studies. Systematic Review

Abstract

Beside partial coverage in three reviews so far (1994, 2009, 2019), there is no review on genotoxic studies dealing with mercury (Hg) and human exposure using the most usual genotoxic assays: sister chromatid exchanges (SCE), chromosomal aberrations (CA), cytochalasin B blocked micronucleus assay (CBMN), and single-cell gel electrophoresis (SCGE or alkaline comet assay). Fifty years from the first Hg genotoxicity study and with the Minamata Convention in force, the genotoxic potential of Hg and its derivatives is still controversial. Considering these antecedents, we present this first systematic literature overview of genotoxic studies dealing with Hg and human exposure that used the standard genotoxic assays. To date, there is not sufficient evidence for Hg human carcinogen classification, so the new data collections can be of great help. A review was made of the studies available (those published before the end of October 2021 on PubMed or Web of Science in English or Spanish language) in the scientific literature dealing with genotoxic assays and human sample exposure ex vivo, in vivo, and in vitro. Results from a total of 66 articles selected are presented. Organic (o)Hg compounds were more toxic than inorganic and/or elemental ones, without ruling out that all represent a risk. The most studied inorganic (i)Hg compounds in populations exposed accidentally, occupationally, or iatrogenically, and/or in human cells, were Hg chloride and Hg nitrate and of the organic compounds, were methylmercury, thimerosal, methylmercury chloride, phenylmercuric acetate, and methylmercury hydroxide.

In vitro analysis of thimerosal genotoxicity and cytotoxicity effect

“…The study found that peripheral blood cultures and, in some cases, oral mucosa epithelial cells were mainly used for genotoxic changes, such as CA and MN. 15 We were used only peripheral blood lymphocytes in our study.…”

The Toxicity of Mercury and Its Chemical Compounds: Molecular Mechanisms and Environmental and Human Health Implications: A Comprehensive Review

“…In addition, mercury exposure can lead to genomic instability, characterized by an increased frequency of mutations and chromosomal aberrations. 9 Several assays, including sister chromatid exchanges (SCE), chromosomal aberrations (CA), cytochalasin B blocked micronucleus test (CBMN), and single-cell gel electrophoresis, are frequently used to determine the genotoxic effect of 77 Magnavita et al, 78 Karri et al, 79 Navarro-Sempere et al, 80 Behzadfar et al, 81 Philibert et al, 82 Chung et al, 83 Li et al 86 Molecular mechanism:…”

“…Mercury-induced genotoxicity may trigger apoptosis as a cellular response to severe DNA damage. In addition, mercury exposure can lead to genomic instability, characterized by an increased frequency of mutations and chromosomal aberrations …”

“…Also, it has to be mentioned that the safe dose of mercury in food is 0.1 μg/kg of body weight, but the actual concentration in most living organisms is higher. A maximum inhalation reference concentration of 0.3 μg/m 3 for atmospheric Hg 0 was previously set by the EPA, as well as reference doses of 0.3 μg/kg and 0.1 μg/kg per day for mercuric chloride and MeHg, respectively . Also, a concentration limit ranging from 0.2 to 1 mg/kg of MeHg in fish was previously set .…”

“…• Free radicals' production • Functional deficiency Wada et al, 101 Rice et al, 102 Gardner et al, 106 Singh, 107,108 Nyland et al, 109 Mishra, 176 Liao et al, 177 Muhammad et al 178 • Mercury inhibits PMN function by reducing its ability to eliminate foreign compounds by suppressing adrenocorticosteroids synthesis, which prevents proper stimulation of PMN formation Lei et al, 121 Pollack et al, 122 Choy et al, 123 Genuis et al, 124 Yoshida, 125 Castoldi et al, 127 Mottet et al 34 Virani et al, 136 Pelch et al, 137 Brocato et al, 138 Maccani et al, 139 Goodrich et al, 140 Zefferino et al, 141 Intarasunanont et al 179 mercury compounds (SCGE or alkaline comet assay). 9 In this regard, Bucio et al 92 used the comet assay to investigate the effect of HgCl 2 on a human fetal liver cell line (WRL-68) to prove the DNA damage by mercury compounds. So, they concluded that raising the mercury concentration and exposure duration increased the nucleus and DNA breakage rate.…”