{"doi":"10.1093/toxsci/kfaa035","title":"Development and Application of TK6-derived Cells Expressing Human Cytochrome P450s for Genotoxicity Testing","abstract":"Metabolism plays a key role in chemical genotoxicity; however, most mammalian cells used for in vitro genotoxicity testing lack effective metabolizing enzymes. We recently developed a battery of TK6-derived cell lines that individually overexpress 1 of 8 cytochrome P450s (CYP1A1, 1A2, 1B1, 2A6, 2B6, 2C9, 2C19, and 3A4) using a lentiviral expression system. The increased expression and metabolic function of each individual CYP in each established cell line were confirmed using real-time PCR, Western blotting, and mass spectrometry analysis; the parental TK6 cells and empty vector (EV) transduced cells had negligible CYP levels. Subsequently, we evaluated these cell lines using 2 prototypical polyaromatic hydrocarbon mutagens, 7,12-dimethylbenz[a]anthracene (DMBA) and benzo[a]pyrene (B[a]P), that require metabolic activation to exert their genotoxicity. DMBA-induced cytotoxicity, phosphorylation of histone H2A.X, and micronucleus formation were significantly increased in TK6 cells with CYP1A1, 1B1, 2B6, and 2C19 expression as compared with EV controls. B[a]P significantly increased cytotoxicity, DNA damage, and chromosomal damage in TK6 cells overexpressing CYP1A1 and 1B1 when compared with EV controls. B[a]P also induced micronucleus formation in TK6 cells expressing CYP1A2. These results suggest that our CYP-expressing TK6 cell system can be used to detect the genotoxicity of compounds requiring metabolic transformation.","journal":"Toxicological Sciences","year":2020,"id":99810,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":29,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9509,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":411356,"name":"Si Chen","orcid":"0000-0002-3228-2837","position":1,"is_corresponding":false},{"id":400720,"name":"Xiaoqing Guo","orcid":"0000-0001-5951-2156","position":2,"is_corresponding":false},{"id":480727,"name":"Qiangen Wu","orcid":"0000-0002-7595-2837","position":3,"is_corresponding":false},{"id":476849,"name":"Ji‐Eun Seo","orcid":"0000-0003-1037-2150","position":4,"is_corresponding":false},{"id":374634,"name":"Lei Guo","orcid":"0000-0002-0402-4152","position":5,"is_corresponding":false},{"id":400722,"name":"Mugimane G. Manjanatha","orcid":"0000-0001-6296-6271","position":6,"is_corresponding":false},{"id":400723,"name":"Tong Zhou","orcid":"0000-0001-9960-1073","position":7,"is_corresponding":false},{"id":400724,"name":"Kristine L. Witt","orcid":"0000-0002-3827-6884","position":8,"is_corresponding":false},{"id":400725,"name":"Nan Mei","orcid":"0000-0002-3501-9014","position":9,"is_corresponding":false},{"id":401365,"name":"Xilin Li","orcid":null,"position":0,"is_corresponding":true}],"reference_count":50,"raw_metadata":null,"created_at":"2026-07-18T22:38:09.754371Z","pmid":"32159784","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}