TABLE 7.
Markers of genotoxicity in cells from exposed individuals.
| Reference | Test system | Population size (n) case/control | As exposure (mean) | Results | Additional information |
|---|---|---|---|---|---|
| Banerjee et al. (2010) |
CA in lymphocytes Serum oxidative stress enzymes activities |
50 exposed (34 with skin lesions; 16 without) 41 unexposed from West Bengal (India) |
Concentration in water (μg/L): exposed, 218.17; unexposed, 6.92; chronic exposure: more than 10 years |
Significantly higher incidence of CA in exposed versus unexposed individuals Catalase and myeloperoxidase activity higher in exposed versus unexposed individuals at low levels of exposure |
Levels of As measured in urine, nails and hair |
| Bartolotta et al. (2011) | MN assay in buccal cells | 27 exposed to high levels, 32 exposed to low levels from rural and urban areas of Argentina | Concentration in water (μg/L): exposed to high levels > 50 versus exposed to low levels < 50, serving as controls | Significant increase of MN frequency in the exposed group of both rural and urban populations versus controls | No effect of age and gender |
| Sampayo‐Reyes et al. (2010) | Alkaline comet assay in peripheral blood leukocytes | 84 exposed (adults and children): low exposed (n = 42); medium exposed (n = 26); high exposed (n = 19) from Northern Mexico |
Concentration in water (μg/L) Low exposed, 12.1; medium exposed, 16; high exposed, 45.6 |
A positive association was found between the level of exposure and DNA breaks (% of DNA in tail) |
Correlation of the total urinary As content of the exposed individuals with the As content in drinking water Influence of AS3MT Met287Thr polymorphism on DNA break induction |
| Banerjee et al. (2013) | MN assay in urothelial cells |
304 exposed 113 unexposed from West Bengal (India) |
Concentration in cooked rice (mg/kg): exposed from > 100 up to > 300; unexposed ≤ 100; not significantly exposed to arsenic through drinking water | Significantly higher MN frequency in all groups with a mean As concentration in cooked rice > 200 μg/kg versus lower exposure group (≤ 100–≤ 200) |
Strong correlation between grouped urinary As and cooked rice As data Information on possible confounding factors available |
| Hinhumpatch et al. (2013) |
8‐oxodG in salivary DNA and urines by HPLC hOGG1 gene expression by RT‐PCR in saliva |
Children: 40 exposed/20 unexposed from Ron Phibul District (Thailand) |
Concentration in water (μg/L): drinking water: exposed 5.66/unexposed 0.4; Non‐drinking water: exposed 39.96/unexposed 2.97; In utero and continuous exposure |
Significantly higher levels of salivary 8‐oxodG in exposed children; levels of urinary 8‐oxodG excretion and salivary hOGG1 expression significantly lower in exposed children | Analysis of As in drinking water, saliva, nails and urines. Information on possible confounding factors available |
| Paul, Das, et al. (2013) | MN assay in urothelial cells and lymphocytes | 189 arsenicosis/171 unexposed from West Bengal (India) recruited at two time points, (2005–06 and 2010–11) |
Concentration in water (μg/L): Exposed: 190.1 (2005–2006)/37.94 (2010–2011) Unexposed: < 10 |
Decrease of As exposure resulted in significant decline of MN frequency in urothelial cells and lymphocytes No changes of MN frequency in unexposed individuals at the two recruitment times |
Decrease of As exposure resulted in significant decline in the number of individuals having dermatological disorders and in the severity of each dermatological outcome |
| Paul, Bhattacharjee, et al. (2013) | MN assay in urothelial cells | 145 exposed/60 unexposed (2004–2005); 128 exposed/54 unexposed (2010–2011) | Concentration in water (μg/L): 348.23 (2004–2005)/ 5.60 (2010–2011) |
Decrease of As exposure resulted in a significant decline in the MN frequency No changes of MN frequency in unexposed individuals at the two recruitment times |
|
| Pei et al. (2013) | 8‐oxodG by Elisa in urines and leukocytes | 75 exposed/12 unexposed from China | Concentration in water (μg/L): exposed from 27.2 to 35.6 from normal to severe skin lesions | Chronic exposure to low levels selectively induces oxidatively induced DNA damage of peripheral blood polymorphonuclear cells | Urinary As levels were increased in the severe skin lesion group compared with the normal group. Information on confounding factors available |
| Harper et al. (2014) |
8‐oxodG in urines by Elisa Protein carbonyls by Elisa in plasma |
378 participants from Bangladesh | Concentration in water (μg/L): five exposure categories from < 10 to > 300 | None of the measures of As exposure was significantly associated with protein carbonyl or 8‐oxodG levels | Water, blood and urinary As concentrations were measured. Information on possible confounding factors available |
| Paul et al. (2014) | MN assay in lymphocytes | 157 exposed (75 WOSL; 82 WSL)/ 88 unexposed individuals from West Bengal (India) | Concentration in water (μg/L): exposed WOSL 186.74; WSL 195.66 / unexposed: 4.37 | Significant increase of MN frequency in both subpopulations of exposed individuals (higher in WSL versus WOSL) versus unexposed individuals |
As levels measured in water, urine, nails, hair and blood samples Promoter hypomethylation of ERCC2 and decrease in CAK activity |
| Dutta et al. (2015) |
Alkaline comet assay in airway cells 8‐oxodG in plasma by Elisa |
142 chronically exposed women/ 131 unexposed women from West Bengal, India | Concentration in water (μg/L): exposed 11–50; unexposed < 10 | Significantly higher levels of DNA breaks (comet tail moment) in airway cells from exposed versus unexposed women. Increased levels of 8‐oxodG in plasma of exposed women | Elevated inflammation markers in exposed women |
| Bandyopadhyay et al. (2016) | MN assay in lymphocytes | Children (5–15 years): 67 exposed/49 unexposed from West Bengal (India) | Concentration in water (μg/L): exposed, 45.01; unexposed, 6.22; chronic exposure: since birth | MN frequency significantly higher in exposed versus unexposed individuals | Significant association of MN frequency in exposed individuals with reduced LINE‐1 methylation |
| Roy et al. (2016) |
MN assay in exfoliated buccal cells Comet assay in lymphocytes |
138 individuals divided into four groups. Group I (n = 54) non chewer, unexposed. Group II (n = 32) chewers, unexposed. Group III (n = 24) exposed, non‐chewers. Group IV (n = 28) chewers, exposed |
Concentration in water (μg/L) exposed Group III, 43; Group IV, 43; unexposed Group I, 2 and Group II, 3 | Statistically significant increase of MN frequency for Group II, III and IV as compared to controls (Group I); Group IV the highest incidence of MN. DNA breaks (% of tail DNA) gradual significant increase among the groups. Strong positive correlation between the exposed population and the frequency of binucleated cells | Amount of chewing tobacco had significant positive correlation with MN frequency and in the percentage of tail DNA |
| Tovar‐Sanchez et al. (2016) | Alkaline comet assay and CA in whole blood samples | 22 exposed, 20 unexposed from Mexico | Concentration in water (μg/L): exposed 60, unexposed (not detected) | DNA breaks (tail length) and CA were positively and significantly correlated with As concentrations in whole blood samples. Terminal deletions registered the highest determination coefficient | Check for metal concentration (Pb, As, Cu, Zn, Cd) in drinking water. As was the only metal with a significant difference in blood samples between exposed and control. Information on confounding factors available |
| Jiménez‐Villarreal et al. (2017) | Two‐tailed comet assay in lymphocytes | 76 exposed, 112 unexposed from Mexico | Concentration in water (μg/L): exposed 14.3/unexposed 7.7 | Significantly higher frequency of DSB (comet tail length) in exposed to higher levels of As versus control group | Information on nutritional status and lifestyle variables |
| Phookphan et al. (2017) | 8‐nitroguanine by Elisa in urines | Children (6–9 years): 40 exposed, 41 unexposed; prenatally and early childhood exposed, from Thailand | Concentration in water (μg/L): 8.38 and 78.05 for drinking and non‐drinking water, respectively. Levels of As in drinking and non‐drinking water in the control sites were 12.5‐ and 13.4‐fold lower | The level of urinary 8‐nitroguanine was significantly higher in exposed newborns and children, by 1.4‐ and 1.8‐fold, respectively | Hypomethylation of inflammatory genes (COX2, EGR1 and SOCS3) |
| Chatterjee et al. (2018) | MN assay in buccal and urothelial cells, and lymphocytes | Children (5–15 years): 68 exposed/52 non exposed from West Bengal (India) | Concentration in water (μg/L) exposed 50.8 and unexposed 6.2; chronic exposure since birth | Significantly higher MN frequency in all the three cell types in As exposed children versus unexposed children | Correlation between urinary As and MN frequency in lymphocytes and urothelial cells |
| Mar Wai et al. (2019) | 8 − oxodG in urines by Elisa | 198 pregnant women in the third trimester of pregnancy from Myanmar | Concentration in water (μg/L): 0.02–198, exposure for at least 6 months | Higher urinary As concentrations were significantly associated with higher 8 − oxodG levels | Urinary As concentrations were significantly correlated with drinking water As concentrations |
| Navasumrit et al. (2019) | 8‐oxodG, 8‐nitroguanine by immunoassays, alkaline comet assay and MN assay in cord blood | 205 pregnant women recruited during 2010–2012 from Haman Province, Vietnam |
Concentration in toenail (μg/g): three groups were identified: low < 0.5, medium 0.5–1 and high > 1 Concentration in water (μg/L): low exposed group < 10; high exposed group ~ 60 |
Maternal toenail As level was significantly associated with all markers of early genetic effects. Cord blood As levels associated with DNA strand breaks (tail length, tail moment, %DNA in tail) and MN frequency |
Cord blood As level significantly increased with maternal As exposure The group of women with high exposure had a significant reduction in arsenic methylation capacity |
| Tsai, Kuo, et al. (2021) | 8‐oxodG and N7‐MeG by LC–MS/MS in urines | 788 participants were enrolled in a prospective cohort study in Taiwan between 1991 and 1994, with follow‐up between 2011 and 2014 | Concentration in well water (μg/L): low < 24.30, high > 24.30; cumulative exposure (concentration in well‐water multiplied by the duration of artesian water consumption) low < 874.2, high > 874.2 | The levels of 8‐oxodG and N7‐MeG have a significantly positive association with cumulative artesian well‐water As exposure and urinary As species levels after adjusting for age, sex and cigarette smoking | Non‐statistically significant mediation effects of 8‐oxodG were observed. Higher risk of bladder cancer for participants with As exposure and urinary 8‐OHdG levels higher than the median |
Abbreviations: 8‐OHdG, 8‐hydroxy‐2′‐deoxyguanosine; 8‐oxodG, 8‐hydroxydeoxyguanosine; As, arsenic; AS3MT, arsenic(III)methyltransferase; CA, chromosomal aberration; CAK, CDK‐activating kinase; Cd, cadmium; COX2, cytochrome c oxidase subunit II; Cu, copper; DNA, deoxyribonucleic acid; DSB, double strand break; EGR1, early growth response factor 1; ERCC2, excision repair cross‐complementation group 2; Elisa, enzyme‐linked immunosorbent assay; HPLC, high‐performance liquid chromatography; hOGG1, human 8‐oxoguanine DNA glycosylase 1; LC–MS/MS, liquid chromatography–tandem mass spectrometry; LINE‐1, long interspersed nucleotide element‐1; MN, micronucleus; n, number; N7‐MeG, N7‐methylguanine; Pb, lead; RT‐PCR, reverse transcriptase‐polymerase chain reaction; SOCS3, suppressor of cytokine signalling 3; WOSL, without skin lesions; WSL, with skin lesions; Zn, zinc.