Two directions that cannot be ignored in the study of endemic fluorosis and endemic arsenicosis in China: long-term exposure to low-dose fluoride and arsenic, and non-target organ damage / 中华地方病学杂志

With the comprehensive implementation of prevention and control measures for endemic fluorosis and endemic arsenicosis in China, and in accordance with the World Health Organization (WHO) recommended drinking water standards and the Chinese standards of allowable daily fluoride intake and limit values of arsenic content in drinking water, Chinese residents have entered the era of low-dose fluoride and arsenic exposure. However, there have been few studies focused on the long-term health effects of exposure to low-dose fluoride and arsenic both domestically and internationally. Further more, study on non-target organs of fluoride and arsenic has been neglected. The conclusions are also inconsistent, and there is an urgent need for systematic study to clarify them. Accordingly, this paper proposes to establish a cohort of people exposed to low-dose fluoride and arsenic, systematically carry out study on the long-term health effects and mechanisms of low-dose fluoride and arsenic exposure, and promote China's prevention and control experience to the "the Belt and Road" countries, in order to provide a scientific basis for the formulation of prevention and control strategies and measures for endemic fluorosis and endemic arsenicosis under the new situation in China.

A survey on the prevalence and associated factors of arsenic poisoning-related skin lesions in an arsenic tailing area in Hunan Province, China / 中华皮肤科杂志

Objective:To investigate epidemiological characteristics of arsenic poisoning-related skin lesions in an arsenic tailing area in Hunan Province.Methods:A cross-sectional study was conducted. From October 2016 to January 2017, all residents aged over 18 years (except pregnant women) were enrolled from 3 villages in Baiyun Town, Shimen County, Hunan Province by using a cluster-sampling method. Demographic information was collected through a face-to-face questionnaire interview. All residents received skin examination performed by professional dermatologists, and blood, urine, and hair samples were collected for the measurement of arsenic levels. Non-conditional logistic regression analysis was performed to analyze factors associated with arsenic poisoning-related skin lesions.Results:A total of 1 092 eligible residents in the arsenic tailing area were recruited in this study, and 756 (69.2%, 95% CI: 66.5%, 72.0%) presented with arsenic poisoning-related skin lesions, including hyperkeratosis, hypo- or hyper-pigmentation. The median ( Q1, Q3) arsenic levels were 0.31 (0.14, 0.74) μg/g in hair samples ( n = 1 079), 0.84 (0.67, 1.10) μg/L in blood samples ( n =1 091), and 60.31 (41.71, 91.52) μg/L in urine samples ( n =1 092). Multivariable analysis showed that the occurrence of arsenic poisoning-related skin lesions was associated with age, residential location, and occupational arsenic exposure history, but was not associated with gender, ethnicity, education levels, migration history, arsenic levels in hair, blood, or urine. Compared with the group aged 18 - 39 years, the group aged 40 - 59 years and the group aged over 60 years showed significantly higher risks of arsenic poisoning-related skin lesions (adjusted OR = 11.34, 95% CI: 5.98, 21.50, P < 0.001; adjusted OR = 71.82, 95% CI: 35.81, 144.05, P < 0.001, respectively). Compared with the residents in the Wangyangqiao village, residents in the Heshan village and Huangchang village showed significantly higher risks of arsenic poisoning-related skin lesions (adjusted OR = 2.89, 95% CI: 2.05, 4.08, P < 0.001; adjusted OR = 4.13, 95% CI: 1.94, 8.78, P < 0.001, respectively). The risk of arsenic poisoning-related skin lesions was significantly higher in residents with occupational exposure history than in those without (adjusted OR = 1.99, 95% CI: 1.04, 3.83, P = 0.039) . Conclusion:Nearly 70% of the residents presented with arsenic poisoning-related skin lesions in an arsenic tailing area in Hunan Province, and the duration and previous degree of arsenic exposure were associated with the risk of arsenic poisoning-related skin lesions.

Basal cell carcinoma-clinico-pathological study in Eastern India in correlation with different risk factors

Objectives: To study the histological variants and mimickers of basal cell carcinoma (BCC) alongwith different risk factors among a group of patients from eastern India. Methods: The specimen for the study was sent by the dermatology department for histopathology after skin biopsy. Results: Out of 42 patients, 15 patients studied were males and the rest of the cases were females. The male to female ratio was 0.55:1. Maximum (15 cases) cases were in the age group of 50–59 years. Apart from sunlight, chronic arsenic exposure is an important risk factor of BCC. Basal cell hyperplasia and squamous cell carcinoma are the histological differential diagnosis of nodular BCC and basosquamous BCC. Conclusion: BCC is a disease of the older age group and with female preponderance in our study. Nodular basal cell carcinoma was the most common histologic type of basal cell carcinoma. The face was the most common site for BCC followed by the scalp. UV radiations and Arsenic do play role in the pathogenesis of BCC. CD10 helps differentiate superficial BCC from basal cell hyperplasia.

Effects of chronic exposure to sodium arsenite on liver damage in rats / 预防医学

Objective@#To examine the effect of chronic exposure to sodium arsenite on liver damages in rats. @*Methods@#Fifty-six healthy adult SD rats (28 males and 28 females) were randomly divided into 4 groups. Rats in the low-, medium- and high-dose groups were given sodium arsenite solutions at doses of 2, 10 and 50 mg/L for successive 24 weeks, while animals in the control group were given deionized water. The rat body and liver weights were measured and the liver coefficient was estimated. The urine arsenic level was detected using atomic fluorescence spectrometry, and hepatic tissue sections were stained with uranium acetate and lead citrate for morphological observations under an electron microscope. @*Results@#The body weights of both male and female rats appeared a tendency towards a rise with the duration of exposure to sodium arsenite (male rat: Wald χ2=3 610.621, P<0.001; female rat: Wald χ2=2 186.217, P<0.001, and there were no significant differences in the rat body weight 24 weeks post-exposure to sodium arsenite in each group, while there was an interaction between time and group (male rat: Wald χ2=15.874, P=0.001; Wald χ2=9.460, P=0.024). There were significant differences in the rat liver weight and liver coefficient in each group (male rat: F=18.964 and 29.968, both P<0.001; female rat: F=11.919 and 15.070, both P<0.001), with the lowest liver weight (10.17±1.15) g and liver coefficient (1.99±0.21)% measured in male rats in the high-dose group, and the highest liver weight (12.91±1.29) g and liver coefficient (4.10±0.56)% in female rats in the high-dose group. The median urine arsenic levels (interquartile range) were 25.60 (30.27), 146.56 (101.06), 1 034.68 (600.06) and 3 796.98 (19 966.89) μg/L in rats in the control, low-dose, medium-dose and high-dose groups, respectively (χ2=50.211, P<0.001), and the urine arsenic level was significantly higher in the medium- and high-dose groups than in the control group (both P<0.001). Hepatic edema was seen in rats in the low- and medium-dose groups, and hepatic edema, focal hepatic cell necrosis, hyperplasia of bile capillaries and peri-bile capillary endolysis were observed in rats in the high-dose group.@*Conclusions@#Chronic exposure to arsenic may cause morphological alterations of rat hepatic tissues, and the rat hepatic damage aggravates with the dose of exposure to arsenic.

The adaptive antioxidant response and diabetogenic effect of chronic arsenic exposure / 中华地方病学杂志

Inorganic arsenic (iAs) is a metalloid element that exists widely in the environment. Chronic iAs exposure may result in various types of cancer and chronic diseases. Although the mechanism of iAs toxicity is complicated, oxidative stress is the most crucial one that has been verified. Accumulating domestic and foreign epidemiological evidence shows that chronic iAs exposure through drinking water is strongly correlated with the prevalence of type 2 diabetes mellitus (T2DM). Mechanistic studies display that iAs exposure causes pancreaticβ-cell dysfunction and insulin resistance. The dynamic balance between reactive oxygen species (ROS) production and antioxidant response is one of the key factors maintaining normal physiological function. ROS plays a significant role in regulating glucose-stimulated insulin secretion and insulin signal transduction. This paper reviews the role of adaptive antioxidant response mediated by nuclear factor E2-related factor 2 ( Nrf2 ) in ROS signaling disorder resulted from chronic iAs exposure, and ROS signaling in the physiological function of pancreatic β-cell.

Effect of arsenic exposure on learning and memory in rat models and its underlying mechanisms / 中华实用儿科临床杂志

Objective To explore the effects of arsenic exposure on learning and memory and its potential mechanism in rats.Methods Water-based arsenic-exposed rat models were established on 4-l0 postnatal days.The experimental animals were divided into 4 groups (10-12 cases in each group):the control group,the 15 μg/L As2O3 water group,the 30 μg/L As2O3 water group,and the 45 μg/L As2O3 water group.Cognitive functions were examined with the Morris water maze,exploratory behavior was detected by the exploratory behavior test.The hippocampus of pups from each experimental group was sectioned at various time points after arsenic exposure.The morphologies and neurogenesis of the neurons in the hippocampus CA1-CA3 region and dentate gyrus (DG) were observed by hematoxylin-eosin staining,Nissl staining,and doublecortin (DCX) immunostaining at different time points after arsenic exposure.Results Compared with the normal control group,the escape latency of the rats in the arsenic-exposed group was prolonged.The average escape latency of the rats in the normal control group,15 μg/L As2O3 group,30 μg/L As2O3 group and45 μg/L As2O3 group were (17.00±9.53) s,(35.89 ±19.81) s,(26.60 ±18.84) s,and (33.79 ±18.08) s,respectively,and the difference among 4 groups was statistically significant (F =3.591,P ＜ 0.05),and the residence time in the original target quadrant was shortened,respectively,(38.93 ± 8.33) s,(36.03 ± 16.25) s,(29.85 ± 9.27) s,and (29.84 ± 10.16) s,respectively,and there was no significant difference among 4 groups (F =1.681,P =0.187).HE staining and Nissl staining showed that pathological changes such as edema,degeneration and necrosis were observed in the hippocampal CA1 area and CA2 area as well as dentate gyrus cells in rats exposed to arsenic in the acute phase.The higher the concentration of arsenic exposure,the more obvious the cell structure disorder was.However,5 weeks after exposure,the pathological changes in hippocampal neurons in the arsenic-exposed group gradually returned to normal.Immunohistochemistry showed that the expressions of DCX in the CA1,CA2 and dentate gyrus of rats exposed to arsenic decreased significantly 24 h after arsenic exposure,especially in the 45 μg/L group.Five weeks after arsenic exposure,there was no expression in the hippocampal CA1-CA3 area,and there was still a small amount of expression in the dentate gyrus.Conclusions Postnatal low-concentration arsenic exposure may impair learning and abnormal germination of neurons in the hippocampal dentate gyrus may be the underlying mechanism.

Impact of Arsenic methylation of population exposed to chronic arsenic through drinking water / 中华地方病学杂志

Objective To investigate the arsenic methylation level of people chronically exposed to different levels of arsenic in drinking water.Methods A cluster sampling method was used to select 874 cases that had drank different concentration arsenic-contaminated water from arsenic endemic area in Bayannaoer City.They were divided into four groups according to arsenic exposure level:control (≤ 10 μg/L),low (＞ 10-50 μg/L),medium (＞ 50-200 μg/L) and high groups (＞ 200 μg/L),146,155,224,349 cases,respectively.The content of arsenic in drinking water and the arsenic species in urine were analyzed by inductively coupled plasma mass spectrometry (ICPMSS) and the results were expressed as median.Results The inorganic arsenic (iAs),monomethylarsonic acid (MMA),dimethylarsinic acid (DMA),and total-arsenic (tAs) in urine of low,medium and high groups increased following increasing of arsenic exposure level (x2 =605.08,609.96,615.83,628.64,all P ＜ 0.017) and iAs％,MMA％ and MMA/DMA significantly increased following increasing of arsenic exposure level (x2 =112.30,56.60,86.47,all P ＜ 0.017).DMA％,PMI and SMI significantly decreased following increasing of arsenic exposure level (x2 =125.80,112.30,86.47,all P ＜ 0.017).In the four groups,iAs％ of female were 11.39％,12.28％,13.47％ and 17.58％,they were significantly lower than those of male's (15.52％,16.19％,17.45％,21.86％,Z =-4.22,-3.79,-4.60,-6.71,all P ＜ 0.05);and DMA％ were 76.95％,74.05％,72.76％,and 68.64％ in the four groups respectively,and the PMI of female were 0.89,0.88,0.87,and 0.82,both DMA％ and PMI were significantly higher than those of male in each group (71.17％,69.39％,67.36％,61.29％,0.84,0.84,0.83,0.78,Z =-4.00,-3.34,-5.50,-7.24,-4.22,-3.79,-4.60,-6.71,all P ＜ 0.05).In control group,arsenic metabolites levels of people were not significantly different in the three age groups (all P ＞ 0.05).Compared to the ≤30 age group,the MMA,DMA and tAs of 31-45 age group increased and DMA,DMA％,PMI of ≥46 age group increased while iAs％ decreased in high group (μg/L:72.71 vs 109.13,307.90 vs 419.50,505.59 vs 684.60,307.90 vs 418.26;64.31％ vs 68.45％,0.79 vs 0.83,20.71％ vs 17.35％,x2 =10.72,10.24,8.20,10.24,9.89,20.96,20.96,all P ＜ 0.017).Compared to the 31-45 age group,DMA％ and PMI of ≥46 age group increased while iAs％ decreased (64.91％ vs 68.45％,0.80 vs 0.83,20.14％ vs 17.35％,x2 =9.89,20.96,20.96,all P ＜ 0.017).Conclusion There is a significant dose response relationship between arsenic metabolites and arsenic exposure level,and arsenic methylation is related to gender and age.

Correlation between blood aryl hydrocarbon receptor, cytochrome P-450 1A1 mRNA expression and skin changes in people with endemic arsenic poisoning / 中华地方病学杂志

Objective Though measuring the expression levels of blood aryl hydrocarbon receptor (AhR) and cytochrome P-450 1A1 (CYP1A1),to explore the relationship between the expression levels and chronic arsenic poisoning induced skin changes.Methods Totally 233 residents were selected in Hanggin Rear Banner arsenic exposure area of Bayannur City,according to water arsenic concentrations,these people were divided into control (＜ 10 μg/L,55 people),low (10-＜ 100 μg/L,47),medium (100-＜ 200 μg/L,45) and high (≥200 pg/L,86) arsenic exposure groups.Real-time PCR was used to detect the expression levels of blood AhR and CYP1A1 mRNA,which were presented in median and quartile [M (Q1-Q3)],and the relationships between their expression levels and keratosis,depigmentation of skin were analyzed.Results The relative expression levels of AhR and CYP1A1 mRNA in high-dose groups were 3.18 × 10-3 (2.42 × 10-3-4.45 × 10-3) and 1.58 × 10-3 (0.80 ×10-3-2.73 × 10-3),which were higher than those in control groups [2.30 × 10-3 (1.53 × 10-3-3.20 × 10-3) and 1.00 × 10-3 (0.59 × 10-3-2.09 × 10-3)],and the difference were statistically significant (all P ＜ 0.05).Compared with control group,the detectable rates of arsenic poisoning,keratosis and depigmentation of skin were higher,and the differences were statistically significant (x2 =20.187,15.848,21.595,all P ＜ 0.05).The detectable rates of arsenic poisoning,keratosis and depigmentation of skin were increased with increase of water arsenic concentrations (x2 =19.012,15.269,16.868,all P ＜ 0.05).Compared with normal [2.54 × 10-3 (1.79 × 10-3-3.43 × 10-3),2.57 × 10-3 (1.78 × 10-3-3.52 × 10-3)],AhR mRNA relative expression levels [4.45 × 10-3 (3.47 × 10-3-8.04 × 10-3),4.45 × 10-3 (4.02 × 10-3-6.25 × 10-3)] of degree Ⅲ keratosis and depigmentation of skin were increased,and the differences were statistically significant (all P ＜ 0.05).Conclusions Chronic arsenic exposure affects the expression level of AhR and CYP1A1 mRNA.Blood AhR mRNA expression may have relationship with endemic arsenic poisoning induced skin change,but blood CYP1A1 mRNA expression may have nothing to do with endemic arsenic poisoning induced skin change.

Association between dyslipidemia and 8-OHdG/Cr among a population exposed to chronic arsenic / 中华流行病学杂志

Objective To explore the association between dyslipidemia and the level of 8-OHdG/Cr in urine among a population exposed to chronic arsenic.Methods Four hundred and seven subjects were randomly selected in an arsenic-affected area in Inner Mongolia.After blood biochemical examination,all the subjects were divided into 4 groups based on the results of total cholesterol (TC),triglycerides (TG),high density lipoprotein cholesterol (HDL-C) and low density lipoprotein cholesterol (LDL-C).The groups consisted of hypercholesterolemia,HDL-C ratio anomaly,combined hypercholesterolemia and HDL-C ratio anomaly,as well as a normal lipid group.Urine samples were collected and 8-OHdG/Cr was measured using the ELISA method.A generalized linear mixed model was used to analyze the association between dyslipidemia and 8-OHdG/Cr.Results The levels of 8-OHdG/Cr as 55.73 (39.90-79.94) ng/mg,58.08 (44.94-69.91) ng/mg,65.28 (49.29-92.95) ng/mg and 51.43 (36.86-68.57)ng/mgin the HDL-C ratio anomaly,hypercholesterolemia,combined hypercholesterolemia and HDL-C ratio anomaly groups and the control group,respectively,which showed significant differences on the levels of 8-OHdG/Cr in the four groups (P=0.006).From the linear regression analysis results showed that the 8-OHdG/Cr level incombined hypercholesterolemia and HDL-C ratio anomaly group was higher (4.25 ± 0.55 ng/mg) than in the control group (3.96 ± 0.55 ng/mg) (P=0.018).After adjusting for important covariates,there was a linear trend between the levels of 8-OHdG/Cr and dyslipidemia (P=0.016).Conclusion Data from our study showed a linear relation between hypercholesterolemia,HDL-C ratio anomaly and the 8-OHdG/Cr level,suggesting that dyslipidemia was associated with oxidative DNA damage among those arsenic-affected people.

Environmental Source of Arsenic Exposure / 예방의학회지

Arsenic is a ubiquitous, naturally occurring metalloid that may be a significant risk factor for cancer after exposure to contaminated drinking water, cigarettes, foods, industry, occupational environment, and air. Among the various routes of arsenic exposure, drinking water is the largest source of arsenic poisoning worldwide. Arsenic exposure from ingested foods usually comes from food crops grown in arsenic-contaminated soil and/or irrigated with arsenic-contaminated water. According to a recent World Health Organization report, arsenic from contaminated water can be quickly and easily absorbed and depending on its metabolic form, may adversely affect human health. Recently, the US Food and Drug Administration regulations for metals found in cosmetics to protect consumers against contaminations deemed deleterious to health; some cosmetics were found to contain a variety of chemicals including heavy metals, which are sometimes used as preservatives. Moreover, developing countries tend to have a growing number of industrial factories that unfortunately, harm the environment, especially in cities where industrial and vehicle emissions, as well as household activities, cause serious air pollution. Air is also an important source of arsenic exposure in areas with industrial activity. The presence of arsenic in airborne particulate matter is considered a risk for certain diseases. Taken together, various potential pathways of arsenic exposure seem to affect humans adversely, and future efforts to reduce arsenic exposure caused by environmental factors should be made.

Environmental Source of Arsenic Exposure / 예방의학회지

Arsenic is a ubiquitous, naturally occurring metalloid that may be a significant risk factor for cancer after exposure to contaminated drinking water, cigarettes, foods, industry, occupational environment, and air. Among the various routes of arsenic exposure, drinking water is the largest source of arsenic poisoning worldwide. Arsenic exposure from ingested foods usually comes from food crops grown in arsenic-contaminated soil and/or irrigated with arsenic-contaminated water. According to a recent World Health Organization report, arsenic from contaminated water can be quickly and easily absorbed and depending on its metabolic form, may adversely affect human health. Recently, the US Food and Drug Administration regulations for metals found in cosmetics to protect consumers against contaminations deemed deleterious to health; some cosmetics were found to contain a variety of chemicals including heavy metals, which are sometimes used as preservatives. Moreover, developing countries tend to have a growing number of industrial factories that unfortunately, harm the environment, especially in cities where industrial and vehicle emissions, as well as household activities, cause serious air pollution. Air is also an important source of arsenic exposure in areas with industrial activity. The presence of arsenic in airborne particulate matter is considered a risk for certain diseases. Taken together, various potential pathways of arsenic exposure seem to affect humans adversely, and future efforts to reduce arsenic exposure caused by environmental factors should be made.

A Case of Primary Cutaneous Mucoepidermoid Carcinoma Developed on the Scrotum / 대한피부과학회지

Mucin producing squamous cell carcinoma (mucoepidermoid carcinoma) is a carcinoma showing squamous and adenomatous differentiation. It is more aggressive than the usual carcinoma of the skin and it must to be evaluated and treated more carefully. We report herein a case of mucoepidermoid carcinoma associated with previous multiple skin cancer. The patient, a 56-year-old male with prior arsenical exposure, presented with a itching irregular marginated ulcer on the left scrotum and other scaly macular erytheinatous skin lesions on the left shoulder and lower back. The histopathological findings from the scrotal lesion showed multiple foci of mucin deposition throughout the squamous cell carcinoma. Special mucin and CEA immunohistochemical staining revealed the epithelial nature of mucin and its glandular structure. We diagnosed this scrotal lesion as mucoepidermoid carcinolna, and it was totally removed by surgical excision.

Detection of p16 gene methylation in population exposed to arsenic in Inner Mongolia / 解放军医学杂志

Objective To investigate the occurrence of p16 gene methylation in the population chronically exposed to arsenic in Inner Mongolia,and to study the molecular mechanisms of carcinogenesis associated with arsenic exposure.Methods The study group was composed of 40 cases of typical arseniasis selected from the epidemic area,and the two control groups consisting respectively of 40 non-arseniasis cases selected from the same epidemic area,and 40 healthy persons enrolled from non-epidemic area.Methylation of p16 gene in the blood specimens were analyzed for all the subjects with MS-PCR techniques,and statistical analysis was performed using chi square test.Results The positive rates of p16 hypermethylation in blood specimens were 65.0%,47.5% and 20.0% respectively in study group and two control groups,and the rate of hypermethylation increased with the increase in arsenic exposure with drinking water in epidemic areas.The positive rate of p16 hypermethylation showed significant differences(P