{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T01:49:41Z","timestamp":1790732981717,"version":"4.1.0"},"reference-count":49,"publisher":"American Chemical Society (ACS)","issue":"12","license":[{"start":{"date-parts":[[2017,12,29]],"date-time":"2017-12-29T00:00:00Z","timestamp":1514505600000},"content-version":"vor","delay-in-days":2676,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2010,12,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Cadmium (Cd) is a carcinogenic heavy metal of environmental concern. Exposure to both Cd and carcinogenic organic compounds, such as polycyclic aromatic hydrocarbons or aromatic amines (AAs), is a common environmental problem. Human arylamine N-acetyltransferases (NATs) are xenobiotic-metabolizing enzymes that play a key role in the biotransformation of AA carcinogens. Changes in NAT activity have long been associated with variations in susceptibility to different cancers in relation with exposure to certain AAs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>We explored the possible interactions between Cd and the NAT-dependent biotransformation of carcinogenic AAs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We exposed purified enzymes, lung epithelial cells, and mouse models to Cd and subsequently analyzed NAT-dependent metabolism of AAs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We found that Cd, at biologically relevant concentrations, impairs the NAT-dependent acetylation of carcinogenic AAs such as 2-aminofluorene (2-AF) in lung epithelial cells. NAT activity was strongly impaired in the tissues of mice exposed to Cd. Accordingly, mice exposed to Cd and 2-AF displayed altered in vivo toxicokinetics with a significant decrease (~ 50%) in acetylated 2-AF in plasma. We found that human NAT1 was rapidly and irreversibly inhibited by Cd [median inhibitory concentration (IC50) \u2248 55 nM; rate inhibition constant (kinact) = 5 \u00d7 104 M\u22121 \u00b7 sec\u22121], with results of acetyl coenzyme A (acetyl-CoA) protection assays indicating that Cd-mediated inhibition was due to the reaction of metal with the active-site cysteine residue of the enzyme. We found similar results for human NAT2, although this isoform was less sensitive to inactivation (IC50 \u2248 1 \u03bcM; kinact = 1 \u00d7 104 M\u22121 \u00b7 sec\u22121).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our data suggest that Cd can alter the metabolism of carcinogenic AAs through the impairment of the NAT-dependent pathway, which may have important toxicological consequences.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1289\/ehp.1002334","type":"journal-article","created":{"date-parts":[[2010,9,1]],"date-time":"2010-09-01T14:28:26Z","timestamp":1283351306000},"page":"1685-1691","source":"Crossref","is-referenced-by-count":21,"title":["Cadmium Alters the Biotransformation of Carcinogenic Aromatic Amines by Arylamine\n                    <i>N<\/i>\n                    -Acetyltransferase Xenobiotic-Metabolizing Enzymes: Molecular, Cellular, and\n                    <i>in Vivo<\/i>\n                    Studies"],"prefix":"10.1021","volume":"118","author":[{"given":"Nilusha","family":"Ragunathan","sequence":"first","affiliation":[{"name":"Universit\u00e9 Paris Diderot-Paris 7, Unit\u00e9 de Biologie Fonctionnelle et Adaptative, Centre National de la Recherche Scientifique, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julien","family":"Dairou","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris Diderot-Paris 7, Unit\u00e9 de Biologie Fonctionnelle et Adaptative, Centre National de la Recherche Scientifique, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elodie","family":"Sanfins","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris Diderot-Paris 7, Unit\u00e9 de Biologie Fonctionnelle et Adaptative, Centre National de la Recherche Scientifique, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florent","family":"Busi","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris Diderot-Paris 7, Unit\u00e9 de Biologie Fonctionnelle et Adaptative, Centre National de la Recherche Scientifique, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christophe","family":"Noll","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris Diderot-Paris 7, Unit\u00e9 de Biologie Fonctionnelle et Adaptative, Centre National de la Recherche Scientifique, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathalie","family":"Janel","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris Diderot-Paris 7, Unit\u00e9 de Biologie Fonctionnelle et Adaptative, Centre National de la Recherche Scientifique, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Marie","family":"Dupret","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris Diderot-Paris 7, Unit\u00e9 de Biologie Fonctionnelle et Adaptative, Centre National de la Recherche Scientifique, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernando","family":"Rodrigues-Lima","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris Diderot-Paris 7, Unit\u00e9 de Biologie Fonctionnelle et Adaptative, Centre National de la Recherche Scientifique, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2010,9,1]]},"reference":[{"key":"2026080513040590000_micit1","volume-title":"Toxicological Profile for Cadmium","author":"Agency for Toxic Substance and Disease 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