{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T23:11:13Z","timestamp":1775862673067,"version":"3.50.1"},"reference-count":42,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2024,12,7]],"date-time":"2024-12-07T00:00:00Z","timestamp":1733529600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institute of Environmental Health Sciences","award":["T32-ES011564"],"award-info":[{"award-number":["T32-ES011564"]}]},{"name":"National Institute of Environmental Health Sciences","award":["P30-ES030283"],"award-info":[{"award-number":["P30-ES030283"]}]},{"name":"National Institute of Environmental Health Sciences","award":["P42-ES023716"],"award-info":[{"award-number":["P42-ES023716"]}]},{"name":"National Institute of Environmental Health Sciences","award":["P20-GM113226"],"award-info":[{"award-number":["P20-GM113226"]}]},{"name":"NIGMS [National Institute of General Medical Sciences]","award":["T32-ES011564"],"award-info":[{"award-number":["T32-ES011564"]}]},{"name":"NIGMS [National Institute of General Medical Sciences]","award":["P30-ES030283"],"award-info":[{"award-number":["P30-ES030283"]}]},{"name":"NIGMS [National Institute of General Medical Sciences]","award":["P42-ES023716"],"award-info":[{"award-number":["P42-ES023716"]}]},{"name":"NIGMS [National Institute of General Medical Sciences]","award":["P20-GM113226"],"award-info":[{"award-number":["P20-GM113226"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>3,4-Dimethylaniline (3,4-DMA) is present in cigarette smoke and widely used as an intermediate in dyes, drugs, and pesticides. Nucleotide excision repair-deficient Chinese hamster ovary (CHO) cells stably transfected with human CYP1A2 and N-acetyltransferase 1 (NAT1) alleles: NAT1*4 (reference allele) or NAT1*14B (the most common variant allele) were utilized to assess 3,4-DMA N-acetylation and hypoxanthine phosphoribosyl transferase (HPRT) mutations, double-strand DNA breaks and reactive oxygen species (ROS). CHO cells expressing NAT1*4 exhibited significantly (p &lt; 0.001) higher 3,4-DMA N-acetylation rates than CHO cells expressing NAT1*14B both in vitro and in situ. In CHO cells expressing CYP1A2 and NAT1, 3,4-DMA caused concentration-dependent increases in reactive oxygen species (ROS), double-stranded DNA damage, and HPRT mutations. CHO cells expressing NAT1*4 and NAT1*14B exhibited concentration-dependent increases in ROS following treatment with 3,4-DMA (linear trend p &lt; 0.001 and p &lt; 0.0001 for NAT1*4 and NAT1*14B, respectively) that were lower than in CHO cells expressing CYP1A2 alone. DNA damage and oxidative stress induced by 3,4-DMA did not differ significantly (p &gt;0.05) between CHO cells expressing NAT1*4 and NAT1*14B. CHO cells expressing NAT1*14B showed higher HPRT mutants (p &lt; 0.05) than CHO cells expressing NAT1*4. These findings confirm 3,4-DMA genotoxicity consistent with potential carcinogenicity.<\/jats:p>","DOI":"10.3390\/biom14121562","type":"journal-article","created":{"date-parts":[[2024,12,9]],"date-time":"2024-12-09T04:01:37Z","timestamp":1733716897000},"page":"1562","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Bioactivation, Mutagenicity, DNA Damage, and Oxidative Stress Induced by 3,4-Dimethylaniline"],"prefix":"10.3390","volume":"14","author":[{"given":"Mariam R.","family":"Habil","sequence":"first","affiliation":[{"name":"Department of Pharmacology & Toxicology, University of Louisville School of Medicine, Louisville, KY 40202, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ra\u00fal A.","family":"Salazar-Gonz\u00e1lez","sequence":"additional","affiliation":[{"name":"Department of Pharmacology & Toxicology, University of Louisville School of Medicine, Louisville, KY 40202, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark A.","family":"Doll","sequence":"additional","affiliation":[{"name":"Department of Pharmacology & Toxicology, University of Louisville School of Medicine, Louisville, KY 40202, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3261-9775","authenticated-orcid":false,"given":"David W.","family":"Hein","sequence":"additional","affiliation":[{"name":"Department of Pharmacology & Toxicology, University of Louisville School of Medicine, Louisville, KY 40202, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,12,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1093\/carcin\/bgp267","article-title":"Monocyclic aromatic amines as potential human carcinogens: Old is new again","volume":"31","author":"Skipper","year":"2010","journal-title":"Carcinogenesis"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"101619","DOI":"10.1016\/j.jwpe.2020.101619","article-title":"A novel method Hybrid Photo-electrocatalytic Oxidation for the treatment of 3,4-dimethyaniline wastewater: Degradation mechanism and synergistic effect","volume":"38","author":"Li","year":"2020","journal-title":"J. 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