Abstract
Arsenic toxicity in humans manifests several outcomes in humans, which include arsenic-induced genomic instability, DNA damage, impaired DNA repair, carcinogenesis, dermatological lesions and other health related problems. Of the 137 million individuals affected, nearly 26 million individuals are in the state of West Bengal, India. Studies have identified dermatological lesions like keratosis, basal cell carcinoma, Bowen’s diseases, squamous cell carcinoma, etc., as key indicators of aggressive arsenic toxicity in humans. Although a large number of individuals are exposed to arsenic but only about 15 to 20 % individuals showed arsenic induced skin lesions. This clearly indicates that genetic susceptibility plays an important role in arsenic susceptibility. Analyses of genetic susceptibility have been carried out to study the prevalence of single nucleotide polymorphisms (SNPs) in number of genes as they might be involved arsenic metabolism and detoxification. It has been observed that a number SNPs in these genes were significantly associated with arsenic induced skin lesions and other health effects. In the present review we try to coalesce the different observations and associations of SNPs with arsenic-induced toxicity, with special emphasis on the study population from West Bengal. We have adopted certain candidate gene approaches to evaluate the association of arsenic-induced toxic outcomes like skin lesions, conjunctival irritations, DNA damage, epimutagenesis, cancer, etc. This review shall be helpful in understanding the importance of genetic make-up of an individual towards evaluating the xenotoxic outcomes, like those in case of arsenic exposure.
Highlights
A global concern, a potent carcinogen and toxic upon chronic exposure, arsenic-induced toxicity in humans is multi-pronged; having a varied spectrum of pathophysiological outcomes
We conducted a study to compare the frequency distribution of chromosomal aberrations (% aberrant cell and CA/cell) between the risk genotype and the reference genotypes at p53 codon 72 locus with individuals without arsenic-induced skin lesions, individuals with keratosis and total population, and we found that the risk genotype containing homozygous arginine (R/R) had shown significantly higher chromosomal aberrations both in form of % aberrant cell and CA/cell in two study groups individually
In our study population of West Bengal, we evaluated the null variants for GSTM1, GSTP1 and GSTT1, where we found a significant association of the GSTM1 null variants with arsenic exposed individuals without skin lesions, indicating of a protective role of GSTM1 null towards incidence of arsenic induced dermatological lesions [49]
Summary
A global concern, a potent carcinogen and toxic upon chronic exposure, arsenic-induced toxicity in humans is multi-pronged; having a varied spectrum of pathophysiological outcomes. SNP analysis of 594 arsenic-induced dermatological cases found a significant association between arsenic metabolic pathway genes with risk of premalignant skin lesions [23]. In a study involving more than 200 arsenic exposed samples from the arsenic affected districts of the state of West Bengal, elaborated that among AS3MT, PNP and GSTO(1/2), only exonic SNP of PNP showed a significant association in developing arsenic-induced dermatological lesions [26].
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