{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T09:28:15Z","timestamp":1785403695926,"version":"3.56.0"},"reference-count":36,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T00:00:00Z","timestamp":1775779200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007197","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P30-ES030283"],"award-info":[{"award-number":["P30-ES030283"]}],"id":[{"id":"10.13039\/100007197","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007197","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P42-ES023716"],"award-info":[{"award-number":["P42-ES023716"]}],"id":[{"id":"10.13039\/100007197","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007197","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P20-GM113226"],"award-info":[{"award-number":["P20-GM113226"]}],"id":[{"id":"10.13039\/100007197","id-type":"DOI","asserted-by":"publisher"}]},{"award":["P30-ES030283"],"award-info":[{"award-number":["P30-ES030283"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"award":["P42-ES023716"],"award-info":[{"award-number":["P42-ES023716"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"award":["P20-GM113226"],"award-info":[{"award-number":["P20-GM113226"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Hydralazine is widely used to treat hypertension during pregnancy and has epigenetic effects in cancer therapy. Cryoplatable human hepatocytes showed concentration-dependent increase in DNA damage response (linear trend p = 0.0069) following 24 h hydralazine treatment. DNA repair-deficient UV5 Chinese hamster ovary (CHO) cell lines expressing human CYP1A2 and either NAT2*4 (reference allele) or NAT2*5 (variant allele) were treated with hydralazine for 24 h. CHO cells expressing NAT2*4 showed a higher acetylation rate than those with NAT2*5 (p &lt; 0.001), whereas CHO cell viability did not differ significantly following hydralazine treatment (p &gt; 0.05). Hydralazine caused a concentration-dependent increase in DNA damage response in the un-transfected UV5 CHO cell line, as well as in each of the UV5 CHO cell lines transfected with human CYP1A2 and\/or NAT2 alleles. CHO cells with CYP1A2 only showed higher DNA damage response from hydralazine compared to cells with CYP1A2\/NAT2*4 or CYP1A2\/NAT2*5 (p &lt; 0.05 and p &lt; 0.0001, respectively), and higher in CYP1A2\/NAT2*4 versus CYP1A2\/NAT2*5 cells (p = 0.0011). Apurinic\/apyrimidinic (AP) sites in CHO cells expressing only CYP1A2 were significantly higher than in the un-transfected UV5 CHO cell line (p &lt; 0.01) and higher in CHO cells expressing CYP1A2\/NAT2*4 compared to CYP1A2\/NAT2*5, but the difference was not significant (p &gt; 0.05). In contrast, ROS levels were reduced following hydralazine treatment in CHO cells with CYP1A2\/NAT2*4 and CYP1A2\/NAT2*5 (p &lt; 0.001 and p &lt; 0.05, respectively). The results of the current study document DNA damage responses associated with hydralazine in human hepatocytes and CHO cells. The DNA damage response was increased following N-hydroxylation by CYP1A2, which competes with N-acetylation by NAT2.<\/jats:p>","DOI":"10.3390\/biom16040562","type":"journal-article","created":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T10:20:16Z","timestamp":1775816416000},"page":"562","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Impact of N-Acetylation on DNA Damage and Oxidative Stress Responses in Mammalian Cells and Human Hepatocytes Treated with Hydralazine"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9205-6076","authenticated-orcid":false,"given":"Mariam R.","family":"Habil","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Toxicology, School of Medicine, University of Louisville, Louisville, KY 40202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Makayla A.","family":"Stephens","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, School of Medicine, University of Louisville, Louisville, KY 40202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-3678-813X","authenticated-orcid":false,"given":"Alexandra A.","family":"Cass","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, School of Medicine, University of Louisville, Louisville, KY 40202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-9428-6655","authenticated-orcid":false,"given":"Elise M.","family":"Mittlestat","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, School of Medicine, University of Louisville, Louisville, KY 40202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-9223-2918","authenticated-orcid":false,"given":"Darbie","family":"Kwon","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, School of Medicine, University of Louisville, Louisville, KY 40202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra","family":"Ellison","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, School of Medicine, University of Louisville, Louisville, KY 40202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8679-2536","authenticated-orcid":false,"given":"J. Calvin","family":"Kouokam","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, School of Medicine, University of Louisville, Louisville, KY 40202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3261-9775","authenticated-orcid":false,"given":"David W.","family":"Hein","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, School of Medicine, University of Louisville, Louisville, KY 40202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/B978-0-12-398339-8.00005-7","article-title":"Arylamine N-acetyltransferases\u2014From drug metabolism and pharmacogenetics to identification of novel targets for pharmacological intervention","volume":"63","author":"Sim","year":"2012","journal-title":"Adv. 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