{"doi":"10.1016/j.etap.2025.104699","title":"Metabolism and genotoxicity of 4,4’-oxydianiline is dependent on N-acetyltransferase 2 genetic polymorphism","abstract":"4,4'-oxydianiline (ODA) is an environmental aromatic amine reasonably anticipated to be a human carcinogen. We investigated ODA genotoxicity and oxidative stress modified by N-acetyltransferase 2 (NAT2) genetic polymorphism in yeast and DNA repair deficient (UV5) Chinese hamster ovary cells (CHO) expressing human NAT2*4 (rapid acetylator allele) or human NAT2*5B (slow acetylator allele) and in cryopreserved human hepatocytes from rapid, intermediate, or slow NAT2 acetylator genotypes. N-acetylation of ODA was both concentration- and time-dependent and significantly higher in yeast and CHO cells expressing NAT2*4 versus NAT2*5B. ODA-induced DNA damage response and reactive oxygen species (ROS/RNS) were significantly higher, while intracellular reduced glutathione (GSH) and oxidized glutathione (GSSG) ratio or mitochondrial integrity were significantly lower in CHO cells expressing NAT2*4 than NAT2*5B. Dose- and NAT2 phenotype-dependent responses also were observed in human cryopreserved human hepatocytes. Our findings have important implications for precise risk assessments following exposures to ODA and azo dye precursors.","journal":"Environmental Toxicology and Pharmacology","year":2025,"id":540908,"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":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9692,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":769018,"name":"J. Wise","orcid":"0000-0002-8878-3841","position":1,"is_corresponding":false},{"id":117877,"name":"Mark A. Doll","orcid":null,"position":2,"is_corresponding":false},{"id":117876,"name":"David W. Hein","orcid":"0000-0003-3261-9775","position":3,"is_corresponding":false},{"id":432390,"name":"Raúl A. Salazar‐González","orcid":"0000-0002-5153-1077","position":0,"is_corresponding":true}],"reference_count":29,"raw_metadata":null,"created_at":"2026-07-19T02:52:42.901627Z","pmid":"40246217","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":[]}