title: Cytogenomics of hexavalent chromium (Cr 6+) exposed cells: a comprehensive review.
abstract: The altered cellular gene expression profile is being hypothesized as the possible molecular basis navigating the onset or progress of various morbidities. This hypothesis has been evaluated here in respect of Cr 6+ induced toxicity. Several studies using gene microarray show selective and strategic dysregulations of cellular genes and pathways induced by Cr 6+. Relevant literature has been reviewed to unravel these changes in different test systems after exposure to Cr 6+ and also to elucidate association if any, of the altered cytogenomics with Cr 6+ induced toxicity or carcinogenicity. The aim was to verify the hypothesis for critical role of altered cytogenomics in onset of Cr 6+ induced biological/clinical effects by identifying genes modulated commonly by the toxicant irrespective of test system or test concentrations/doses, and by scrutinizing their importance in regulation of the flow of mechanistically linked events crucial for resultant morbidities. Their probability as biomarkers to monitor the toxicant induced biological changes is speculative. The modulated genes have been found to cluster under the pathways that manage onset of oxidative stress, DNA damage, apoptosis, cell-cycle regulation, cytoskeleton, morphological changes, energy metabolism, biosynthesis, oncogenes, bioenergetics, and immune system critical for toxicity. In these studies, the identity of genes has been found to differ remarkably; albeit the trend of pathways' dysregulation has been found to remain similar. We conclude that the intensity of dysregulation of genes or pathways involved in mechanistic events forms a sub-threshold or threshold level depending upon the dose and type (including speciation) of the toxicant, duration of exposure, type of target cells, and niche microenvironment of cells, and the intensity of sub-threshold or threshold level of the altered cytogenomics paves way in toxicant exposed cells eventually either to opt for reversal to differentiation and growth, or to result in toxicity like dedifferentiation and apoptosis, respectively.
authors.forename: Akanksha
authors.initials: A
authors.lastname: Nigam
authors.forename: Shivam
authors.initials: S
authors.lastname: Priya
authors.forename: Preeti
authors.initials: P
authors.lastname: Bajpai
authors.affiliation: Environmental Carcinogenesis Division, CSIR-Indian Institute of Toxicology Research, Lucknow, India.
authors.forename: Sushil
authors.initials: S
authors.lastname: Kumar
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology; D002468:Cell Physiological Phenomena / Q000187:drug effects*; D002477:Cells / Q000378:metabolism*; D002857:Chromium / Q000633:toxicity*; D003582:Cytogenetics / Q000379:methods*; D004305:Dose-Response Relationship, Drug; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology
chemical_list: D015415:Biomarkers; D002857:Chromium; C074702:chromium hexavalent ion