Effect of sodium arsenite on peripheral lymphocytes in vitro: individual susceptibility among a population exposed to arsenic through the drinking water

Arsenic (As) contamination in ground water has affected more than 19 countries. Approximately 36 million people in the Bengal delta alone are exposed to this toxicant via drinking water (>50 mg/l) and are at potential health risk. Chronic ingestion of As via drinking water is associated with occurrence of skin lesions, cancer and other arsenicinduced diseases in West Bengal, India. An in vitro cytogenetic study was performed utilizing chromosomal aberrations (CA) in lymphocytes treated with sodium arsenite (0±5 mM) in six symptomatic (having arsenicrelated skin lesions) individuals, six age- and sex-matched As-exposed asymptomatic (no arsenic-related skin lesions) individuals and six control individuals with similar socioeconomic status residing in non-affected districts of West Bengal with no evidence of As exposure. The mean As content in nails and hair was 9.61 and 5.23 mg/g in symptomatic, 3.48 and 2.17 mg/g in asymptomatic and 0.42 and 0.33 mg/g in the control individuals, respectively. The main aim of our study was to determine whether genotoxic effects differed in the lymphocytes of the control (no exposure to arsenic), asymptomatic and symptomatic individuals after in vitro treatment with sodium arsenite. Although both the exposed groups had chronic exposure to As through the drinking water, individuals with skin lesions accumulated more As in their nails and hair and excreted less in urine (127.80 versus 164.15 mg/l). The results show that sodium arsenite induced a signiÆcantly higher percentage of aberrant cells in the lymphocytes of control individuals than in the lymphocytes of both the exposed groups. Within the two exposed groups As induced higher incidences of CA in the symptomatic than the asymptomatic individuals. These results suggest that asymptomatic individuals have relatively lower sensitivity and susceptibility to induction of genetic damage by As compared with the symptomatic individuals

Chromosomal Aberrations in Arsenic-Exposed Human Populations: A Review With Special Reference to a Comprehensive Study in West Bengal, India

For centuries arsenic has played an important role in science, technology, and medicine. Arsenic for its environmental pervasiveness has gained unexpected entrance to the human body through food, water and air, thereby posing a great threat to public health due to its toxic effect and carcinogenicity. Thus, in modern scenario arsenic is synonymous with “toxic” and is documented as a paradoxical human carcinogen, although its mechanism of induction of neoplasia remains elusive. To assess the risk from environmental and occupational exposure of arsenic, in vivo cytogenetic assays have been conducted in arseniasis-endemic areas of the world using chromosomal aberrations (CA) and sister chromatid exchanges (SCE) as biomarkers in peripheral blood lymphocytes. The primary aim of this report is to critically review and update the existing in vivo cytogenetic studies performed on arsenic-exposed populations around the world and compare the results on CA and SCE from our own study, conducted in arsenic-endemic villages of North 24 Parganas (district) of West Bengal, India from 1999 to 2003. Based on a structured questionnaire, 165 symptomatic (having arsenic induced skin lesions) subjects were selected as the exposed cases consuming water having a mean arsenic content of 214.96 Ìg/l. For comparison 155 age-sex matched control subjects from an unaffected district (Midnapur) of West Bengal were recruited. Similar to other arsenic exposed populations our population also showed a significant difference (P ! 0.01) in the frequencies of CA and SCE between the cases and control group. Presence of substantial chromosome damage in lymphocytes in the exposed population predicts an increased future carcinogenic risk by this metalloid

Association of specific p53 polymorphisms with keratosis in individuals exposed to arsenic through drinking water in West Bengal, India

Although, more than six million people are endemically exposed to inorganic arsenic in West Bengal, India by drinking heavily contaminated groundwater, only about 300,000 people show arsenic induced skin lesions. This suggests that genetic variability plays an important role in arsenic induced skin lesions and skin cancers. Arsenic induced keratosis is considered as a possible precancerous state of in situ carcinoma. Several reports have suggested the role of p53 polymorphisms as potential marker for risk assessment of different types of cancers. This prompted us to study the association of three p53 polymorphisms with arsenic induced keratosis in a population exposed to arsenic through drinking water. A total of 366 unrelated individuals (177 individuals with arsenic induced keratosis and 189 individuals with no arsenic induced skin lesions) were recruited from North 24 Parganas, Nadia and Murshidabad districts between January 2003 and February 2005 for the study of the genotypic distribution of three p53 polymorphisms (16 bp duplication at intron 3, codon 72 Arg/Pro and G > A at intron 6 [nt 13,494]) by PCR-RFLP. The arginine homozygous genotype at codon 72, and homozygous genotype of no duplication polymorphism at intron 3 were over represented in the individuals with keratosis compared with individuals with no skin lesions (OR = 2.086; 95% CI = 1.318–3.299 and OR = 2.086; 95% CI = 1.257–3.457, respectively). This study indicates that individuals carrying the arginine homozygous genotype at codon 72, and/or no duplication homozygous genotype at intron 3 are at risk for the development of arsenic induced keratosis

Enhanced Frequency of Micronuclei in Individuals Exposed to Arsenic Through Drinking Water in West Bengal, India

InWest Bengal, India arsenic in ground water has been found to be above the maximum permissible limit in seven districts covering an area of 37,493 km2. In the present study, evaluation of the micronuclei (MN) formation in oral mucosa cells, urothelial cells and peripheral blood lymphocytes was carried out in the symptomatic individuals exposed to arsenic through drinking water. Forty five individuals with cutaneous signs of arsenicism from four affected districts (368.11�g/l of As in drinking water) were considered as the exposed group and 21 healthy individuals with no symptoms of arsenic poisoning and residing in two unaffected districts (5.49�g/l of As) were considered as controls. The exposed and control groups had similar age distribution and socioeconomic status. Standardised questionnaires were utilised and medical examination was conducted to ascertain exposure history, sociodemographic characteristics, diet, health, medication, addiction and chief symptoms in the study participants. Arsenic exposure was confirmed by measuring the arsenic content in the drinking water, nails, hair and urine samples from the volunteers. Arsenic contents in the urine, nail and hair in the exposed group were 24.45�g/l, 12.58 and 6.97�g/g, respectively which were significantly high in comparison to corresponding control group values of 4.88�g/l, 0.51 and 0.34�g/g, respectively. Exposed individuals showed a statistically significant increase in the frequency of MN in oral mucosa, urothelial cells and lymphocytes (5.15, 5.74 and 6.39/1000 cells, respectively) when compared with the controls (0.77, 0.56 and 0.53/1000 cells, respectively). Thus, the above results indicate that the symptomatic individuals exposed to arsenic through drinking water in this region have significant cytogenetic damage. © 2002 Elsevier Science B.V