{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,18]],"date-time":"2026-01-18T01:11:51Z","timestamp":1768698711810,"version":"3.49.0"},"reference-count":21,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2020,4]]},"abstract":"\n Arylamine\n N<\/jats:italic>\n -acetyltransferases are xenobiotic-metabolizing enzymes responsible for detoxification of many drugs and carcinogens. Two\n N<\/jats:italic>\n -acetyltransferase proteins (NAT1 and NAT2) are expressed in humans and they both\n N<\/jats:italic>\n -acetylate aromatic amine carcinogens such as 4-aminobiphenyl. Arylamines such as 4-aminobiphenyl represent a large class of chemical carcinogens. Exposure to 4-aminobiphenyl occurs in the chemical, dye and rubber industries as well as in hair dyes, paints, and cigarette smoke. NAT2 is subject to a genetic polymorphism resulting in rapid, intermediate and slow acetylator phenotypes. We investigated the role of the NAT2 genetic polymorphisms on the\n N<\/jats:italic>\n -acetylation of 4-aminobiphenyl in cryopreserved human hepatocytes in which NAT2 genotype and deduced phenotype were determined. Differences in sulfamethazine (selectively\n N<\/jats:italic>\n -acetylated via NAT2) and 4-aminobiphenyl (\n N<\/jats:italic>\n -acetylated by both NAT1 and NAT2)\n N<\/jats:italic>\n -acetylation rates among rapid, intermediate, and slow NAT2 acetylator genotypes were tested for significance by one-way analysis of variance.\n In vitro<\/jats:italic>\n 4-aminobiphenyl\n N<\/jats:italic>\n -acetyltransferase activities differed significantly between rapid, intermediate and slow acetylators at 10 \u00b5M (\n P<\/jats:italic>\n = 0.0102) or 100 \u00b5M (\n P<\/jats:italic>\n = 0.0028).\n N<\/jats:italic>\n -acetylation of 4-aminobiphenyl\n in situ<\/jats:italic>\n also differed significantly between human hepatocytes from rapid, intermediate, and slow acetylators at 10 \u00b5M (\n P<\/jats:italic>\n = 0.0015) and 100 \u00b5M (\n P<\/jats:italic>\n = 0.0216). A gene dose-response relationship was exhibited as intermediate acetylators catalyzed 4-aminobiphenyl\n N<\/jats:italic>\n -acetylation both\n in vitro<\/jats:italic>\n and\n in situ<\/jats:italic>\n at rates arithmetically between rapid and slow acetylators. In conclusion,\n N<\/jats:italic>\n -acetylation of 4-aminobiphenyl is NAT2 genotype-dependent in human hepatocytes. These results suggest refinement of the exposure limit and safety for arylamine carcinogens according to NAT2 genotype.\n <\/jats:p>","DOI":"10.1097\/fpc.0000000000000394","type":"journal-article","created":{"date-parts":[[2019,12,31]],"date-time":"2019-12-31T15:51:49Z","timestamp":1577807509000},"page":"61-65","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":10,"title":["N-acetyltransferase 2 acetylator genotype-dependent N-acetylation of 4-aminobiphenyl in cryopreserved human hepatocytes"],"prefix":"10.1097","volume":"30","author":[{"given":"Mariam R.","family":"Habil","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Toxicology and James Graham Brown Cancer Center, University of Louisville School of Medicine, Louisville, Kentucky, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark A.","family":"Doll","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology and James Graham Brown Cancer Center, University of Louisville School of Medicine, Louisville, Kentucky, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David W.","family":"Hein","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology and James Graham Brown Cancer Center, University of Louisville School of Medicine, Louisville, Kentucky, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"276","reference":[{"key":"R1-20251204","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1097\/FPC.0000000000000062","article-title":"PharmGKB summary: very important pharmacogene information for N-acetyltransferase 2.","volume":"24","author":"McDonagh","year":"2014","journal-title":"Pharmacogenet Genomics"},{"key":"R2-20251204","doi-asserted-by":"crossref","first-page":"540","DOI":"10.1124\/jpet.110.168567","article-title":"Codominant expression of N-acetylation and O-acetylation activities catalyzed by N-acetyltransferase 2 in human hepatocytes.","volume":"334","author":"Doll","year":"2010","journal-title":"J Pharmacol Exp Ther"},{"key":"R3-20251204","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/j.pharmthera.2019.05.004","article-title":"Primary aromatic amines and cancer: novel mechanistic insights using 4-aminobiphenyl as a model carcinogen.","volume":"200","author":"Wang","year":"2019","journal-title":"Pharmacol Ther"},{"key":"R5-20251204","first-page":"29","article-title":"Molecular genetics and epidemiology of the NAT1 and NAT2 acetylation polymorphisms.","volume":"9","author":"Hein","year":"2000","journal-title":"Cancer Epidemiol Biomarkers Prev"},{"key":"R6-20251204","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/j.abb.2007.05.018","article-title":"Hair dye use, meat intake, and tobacco exposure and presence of carcinogen-DNA adducts in exfoliated breast ductal epithelial 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