{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T19:41:21Z","timestamp":1771011681019,"version":"3.50.1"},"reference-count":33,"publisher":"Walter de Gruyter GmbH","issue":"9","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2000,9,18]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Individual risk of toxicity or cancer reflects the amount\nof exposure to environmental agents, combined with\none's underlying genetic predisposition. More than six\ndozen human ecogenetic polymorphisms have been\ndescribed; whereas some of these have been demonstrated\nto be associated with altered risks of toxicity or\ncancer, others presently remain equivocal and require\nfurther study. Thus, genetic differences in the regulation,\nexpression and activity of \u201cenvironmental susceptibility\ngenes\u201d can be decisive in defining susceptibility\nto toxicity or cancer.<\/jats:p>\n               <jats:p>\u201cDrug-metabolizing enzymes\u201d (DMEs) are regarded\nas one class of environmental susceptibility genes.\nDME genes have actually existed on this planet for\nmore than 2.5 billion years, and might more appropriately\nbe named \u201ceffector-metabolizing enzymes.\u201d Receptors\ncontrolling DME levels have been called \u201cDME\nreceptors.\u201d DMEs have functioned in many critical life\nprocesses in prokaryotes and, more recently, in countless\nbasic functions in plants and animals\u2014events that\nevolved long before the existence of pharmaceutical\ncompanies and apothecaries. DME genes exist in every\neukaryotic cell and probably in all prokaryotes. Virtually\nall environmental agents act as either agonists or\nantagonists\u2014in competing with endogenous ligands\nthat bind to DME receptors and\/or competing as substrates\nfor the DMEs. Over the past decade it has become\nclear that each of us has our own \u201cindividual fingerprint\u201d\nof unique alleles coding for DMEs. The\nunderlying genetic predisposition of each patient will\nreflect combinations of poor- and extensive-metabolizer\nphenotypes; if these enzymes cooperate in the\nsame metabolic pathway for any given drug or environmental\nagent, such ecogenetic variability might be\nsynergistic and lead to as much as 30- or &gt;40-fold differences\nin activation or degradation. The end result\ncan be large interindividual differences in risk of environmentally\ncaused toxicity or cancer.<\/jats:p>","DOI":"10.1515\/cclm.2000.124","type":"journal-article","created":{"date-parts":[[2004,10,22]],"date-time":"2004-10-22T10:39:26Z","timestamp":1098441566000},"page":"857-861","source":"Crossref","is-referenced-by-count":35,"title":["Drug-Metabolizing Enzymes, Polymorphisms and Interindividual Response to Environmental Toxicants"],"prefix":"10.1515","volume":"38","author":[{"given":"Daniel W.","family":"Nebert","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"374","published-online":{"date-parts":[[2005,6,1]]},"reference":[{"key":"p_1","first-page":"52","volume":"12","author":"Vogel F","year":"1959","journal-title":"Ergeb Inn Med Kinderheilkd"},{"key":"p_2","doi-asserted-by":"publisher","DOI":"10.1097\/00008571-199712000-00001"},{"key":"p_3","doi-asserted-by":"publisher","DOI":"10.1126\/science.281.5384.1820"},{"key":"p_4","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.pharmtox.39.1.19"},{"key":"p_5","doi-asserted-by":"publisher","DOI":"10.1034\/j.1399-0004.1999.560401.x"},{"key":"p_7","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.pharmtox.39.1.67"},{"key":"p_8","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-2952(99)00310-X"},{"key":"p_9","doi-asserted-by":"publisher","DOI":"10.1089\/dna.1996.15.273"},{"key":"p_10","doi-asserted-by":"publisher","DOI":"10.1038\/347709a0"},{"key":"p_11","doi-asserted-by":"publisher","DOI":"10.1210\/mend-5-9-1203"},{"key":"p_12","doi-asserted-by":"publisher","DOI":"10.1016\/0006-2952(94)90434-0"},{"key":"p_13","first-page":"265","volume":"60","author":"Nebert DW","year":"1997","journal-title":"Am J Hum Genet"},{"key":"p_14","doi-asserted-by":"publisher","DOI":"10.1097\/00008571-199412000-00001"},{"key":"p_15","doi-asserted-by":"publisher","DOI":"10.1038\/46816"},{"key":"p_16","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1999.1287"},{"key":"p_17","first-page":"63","volume":"12","author":"Nebert DW","year":"1994","journal-title":"Progr Liver Dis"},{"key":"p_18","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1998.9519"},{"key":"p_19","doi-asserted-by":"publisher","DOI":"10.1126\/science.7569889"},{"key":"p_20","doi-asserted-by":"publisher","DOI":"10.1126\/science.7892601"},{"key":"p_21","doi-asserted-by":"publisher","DOI":"10.1101\/gad.12.9.1269"},{"key":"p_22","doi-asserted-by":"publisher","DOI":"10.1126\/science.212.4497.927"},{"key":"p_23","doi-asserted-by":"publisher","DOI":"10.1006\/abbi.1994.1175"},{"key":"p_24","first-page":"1","volume":"25","author":"Kalow W","year":"1994","journal-title":"Advanc Drug Res"},{"key":"p_25","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.91.6.1983"},{"key":"p_27","doi-asserted-by":"publisher","DOI":"10.1097\/00008571-200006000-00001"},{"key":"p_29","doi-asserted-by":"publisher","DOI":"10.1016\/0168-9525(90)90174-5"},{"key":"p_30","doi-asserted-by":"publisher","DOI":"10.1016\/S1084-8592(99)80006-X"},{"key":"p_31","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199803053381004"},{"key":"p_32","doi-asserted-by":"publisher","DOI":"10.1086\/302156"},{"key":"p_33","doi-asserted-by":"publisher","DOI":"10.1086\/302681"},{"key":"p_34","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/6.4.641"},{"key":"p_35","doi-asserted-by":"publisher","DOI":"10.1038\/370216a0"},{"key":"p_36","doi-asserted-by":"publisher","DOI":"10.1086\/301982"}],"container-title":["cclm"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.degruyter.com\/document\/doi\/10.1515\/CCLM.2000.124\/xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.degruyter.com\/document\/doi\/10.1515\/CCLM.2000.124\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,3,14]],"date-time":"2022-03-14T14:44:01Z","timestamp":1647269041000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.degruyter.com\/document\/doi\/10.1515\/CCLM.2000.124\/html"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2000,9,18]]},"references-count":33,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2005,6,1]]},"published-print":{"date-parts":[[2000,9,18]]}},"alternative-id":["10.1515\/CCLM.2000.124"],"URL":"https:\/\/doi.org\/10.1515\/cclm.2000.124","relation":{},"ISSN":["1434-6621"],"issn-type":[{"value":"1434-6621","type":"print"}],"subject":[],"published":{"date-parts":[[2000,9,18]]}}}