title: DNA repair deficiency leads to susceptibility to develop arsenic-induced premalignant skin lesions.
abstract: In West Bengal, India, although more than 6 million people are exposed to arsenic through drinking water, only 15-20% showed arsenic-induced skin lesions, including premalignant hyperkeratosis. This indicates toward some factors that confer susceptibility to arsenic-induced carcinogenicity. In this work, we wanted to explore whether differences in DNA repair capacity could impart arsenic-induced carcinogenicity, through Comet assay, chromosomal aberration (CA) assay and challenge assay. Sixty arsenic exposed (30 individuals with arsenic-induced premalignant hyperkeratosis and 30 without skin lesion, but drinking similar arsenic contaminated water) and 30 arsenic unexposed individuals were recruited as study participants. Alkaline comet assay, and challenge assay were carried out in whole blood and CA study in lymphocytes to find out the DNA damage and DNA repair capacity in both hyperkeratotic and without skin lesion individuals. DNA damage as well as CA were found to be significantly higher in the arsenic-exposed individuals compared to unexposed individuals (p < 0.001). Within the exposed group, there was no significant difference as far as the level of DNA damage is concerned (p > 0.05), but CA was significantly higher in exposed individuals with hyperkeratosis than exposed individuals without hyperkeratosis (p < 0.01). Challenge assay showed that upon induction of DNA damage, the repair capacity in the exposed individuals with premalignant hyperkeratosis is significantly less (p < 0.001) than that of individuals without skin lesion, although the basal level of DNA damage was similar in both. Thus, the deficiency in DNA repair capacities in the hyperkeratotic individuals emerges as a prime contender for arsenic carcinogenicity.
authors.affiliation: Molecular and Human Genetics Division, Indian Institute of Chemical Biology, Kolkata, India.
authors.forename: Mayukh
authors.initials: M
authors.lastname: Banerjee
authors.affiliation: Department of Dermatology, Nil Ratan Sircar Medical College and Hospital, Kolkata 700 014, India.
authors.forename: Nilendu
authors.initials: N
authors.lastname: Sarma
authors.affiliation: Centre of Advanced Study, Department of Botany, University of Calcutta, Kolkata, India.
authors.forename: Rupanwita
authors.initials: R
authors.lastname: Biswas
authors.affiliation: Molecular and Human Genetics Division, Indian Institute of Chemical Biology, Kolkata, India.
authors.forename: Jyoeeta
authors.initials: J
authors.lastname: Roy
authors.affiliation: Centre of Advanced Study, Department of Botany, University of Calcutta, Kolkata, India.
authors.forename: Anita
authors.initials: A
authors.lastname: Mukherjee
authors.affiliation: Molecular and Human Genetics Division, Indian Institute of Chemical Biology, Kolkata, India.
authors.forename: Ashok K
authors.initials: AK
authors.lastname: Giri
mesh_terms: D000328:Adult; D001151:Arsenic / Q000009:adverse effects*; D002273:Carcinogens; D004249:DNA Damage / Q000187:drug effects; D004260:DNA Repair / Q000187:drug effects*; D004781:Environmental Exposure / Q000009:adverse effects*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007194:India / Q000453:epidemiology; D007642:Keratosis / Q000139:chemically induced / Q000453:epidemiology / Q000209:etiology* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D011230:Precancerous Conditions / Q000139:chemically induced / Q000453:epidemiology / Q000209:etiology* / Q000235:genetics; D012878:Skin Neoplasms / Q000139:chemically induced / Q000453:epidemiology / Q000209:etiology* / Q000235:genetics; D014881:Water Supply
chemical_list: D002273:Carcinogens; D001151:Arsenic