title: Mitochondrial genome variations among arsenic exposed individuals and potential correlation with apoptotic parameters.
abstract: Exposure to arsenic (As) causes serious health hazards. Therefore, there is a sustained effort to understand the molecular basis of the risk posed by the toxicant. It has been reported that apoptotic changes ensue on exposure to As. To investigate the molecular basis of such changes, we sequenced the entire mitochondrial (mt) genome from PBMC of a subset of these individuals (As-exposed=16 and unexposed=18) using Affymetrix platform. Our analysis revealed that As exposure does not induce large-scale mt-DNA variations, but that specific deleterious changes could induce mt dysfunction. A Glu115Ter mutation as well as 17 other in silico predicted deleterious variants were identified exclusively in exposed individuals. The number of variants in mt Complex I in As-exposed individuals was positively correlated with their respective intracellular ROS level. In addition, the extent of potentially damaging variants in As-exposed individuals had significant positive correlation to the degree of G0 /G1 cell cycle arrest.
authors.affiliation: Molecular and Human Genetics Division, CSIR-Indian Institute of Chemical Biology, Kolkata, 700032, India.
authors.forename: Sharmistha
authors.initials: S
authors.lastname: Sinha
authors.forename: Ashok K
authors.initials: AK
authors.lastname: Giri
authors.forename: Rukhsana
authors.initials: R
authors.lastname: Chowdhury
authors.forename: Kunal
authors.initials: K
authors.lastname: Ray
mesh_terms: D017209:Apoptosis / Q000187:drug effects / Q000235:genetics*; D001151:Arsenic / Q000633:toxicity*; D016022:Case-Control Studies; D014644:Genetic Variation; D054629:Genome, Mitochondrial / Q000187:drug effects*; D006801:Humans; D009154:Mutation; D017382:Reactive Oxygen Species / Q000097:blood
chemical_list: D017382:Reactive Oxygen Species; D001151:Arsenic
keywords: apoptosis; arsenic; mitochondria; mutation