title: Validation of a human cell based high-throughput genotoxicity assay 'Anthem's Genotoxicity screen' using ECVAM recommended lists of genotoxic and non-genotoxic chemicals.
abstract: A novel high throughput-enabled human cell based screen, Anthem's Genotoxicity screen, was developed to achieve higher specificity for predicting in vivo genotoxins by an in vitro method. The assay employs engineered human colon carcinoma cell line; HCT116 cells that are stably engineered with three promoter-reporter cassettes such that an increased reporter activity reflects the activation of associated signaling events in a human cell. The current study focuses on the evaluation of sensitivity and specificity of Anthem's Genotoxicity screen using 62 compounds recommended by the European Centre for the Validation of Alternative Methods (ECVAM). The concordance of Anthem's Genotoxicity screen with in vivo tests was 95.5% with sensitivity of 95.2% and specificity of 95.7%. Thus Anthem's Genotoxicity screen, a high-throughput mechanism based genotox indicator test can be employed by a variety of industries for rapid screening and early detection of potential genotoxins.
authors.affiliation: Anthem Biosciences Pvt. Ltd., #49 Canara Bank Road, Bommasandra Industrial Area, Bommasandra, Electronic City Phase I, Bangalore 560 099, India.
authors.forename: Lakshmi
authors.initials: L
authors.lastname: Rajakrishna
authors.forename: Salini
authors.initials: S
authors.lastname: Krishnan Unni
authors.forename: Madhuri
authors.initials: M
authors.lastname: Subbiah
authors.forename: Sathish
authors.initials: S
authors.lastname: Sadagopan
authors.forename: Ayyappan R
authors.initials: AR
authors.lastname: Nair
authors.forename: Ravindra
authors.initials: R
authors.lastname: Chandrappa
authors.forename: Ganesh
authors.initials: G
authors.lastname: Sambasivam
authors.forename: Sunil Kumar
authors.initials: SK
authors.lastname: Sukumaran
mesh_terms: D003110:Colonic Neoplasms / Q000378:metabolism*; D015195:Drug Design; D004353:Drug Evaluation, Preclinical / Q000379:methods; D064420:Drug-Related Side Effects and Adverse Reactions / Q000175:diagnosis; D017930:Genes, Reporter; D045325:HCT116 Cells; D057166:High-Throughput Screening Assays / Q000379:methods*; D006801:Humans; D009152:Mutagenicity Tests / Q000379:methods*; D009153:Mutagens / Q000633:toxicity*; D012680:Sensitivity and Specificity; D013997:Time Factors
chemical_list: D009153:Mutagens
keywords: ECVAM; GADD153; High-throughput; Human cell based; In vitro genotoxicity screen; Reporter based screen; p21; p53