title: Induced CYP1A2 activity as a phenotypic biomarker in humans highly exposed to certain PCBs/PCDFs.
abstract: Polychlorinated biphenyls (PCBs), dibenzo-p-dioxins (PCDDs), and dibenzofurans (PCDFs) continue to be a worldwide public health concern due to their levels in the environment and humans, and associated adverse health effects. In animals, one of the most sensitive effects of physiologically significant body burdens has been the induction of cytochrome P450 1 (CYP1) family of enzymes. This study examined the capacity of CYP1 enzyme induction to be a biomarker of exposure to a mixture of PCBs and PCDFs and of adverse human health effects. We followed a group of people highly exposed to PCBs and PCDFs due to accidental ingestion of contaminated rice oil, the Yucheng cohort. A total of 174 Yucheng and 134 control subjects were studied. The caffeine breath test, a monitor of CYP1A2 activity, was conducted, and its results were compared to serum levels of chemicals and the subjects' medical history. Total dioxin serum toxic equivalency (TEQ) in the Yucheng cohort and their controls were 577 +/- 393 ppt lipid and 21 ppt lipid, respectively. CYP1A2 activity was elevated in Yucheng subjects more than 2-fold and correlated with serum TEQ (R2= 0.62). Manifestations like chloracne, fingernail abnormalities, and headaches were well predicted by P4501A2 activity. It is concluded that CYP1A2 induction seen in the Yucheng cohort is an excellent biomarker of exposure and human health effects in individual subjects and cohort.
authors.affiliation: Center for Child and Reproductive Environmental Health, Department of Pediatrics, Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey, USA.
authors.forename: George H
authors.initials: GH
authors.lastname: Lambert
authors.forename: Larry L
authors.initials: LL
authors.lastname: Needham
authors.forename: Wayman
authors.initials: W
authors.lastname: Turner
authors.forename: Te Jen
authors.initials: TJ
authors.lastname: Lai
authors.forename: Donald G
authors.initials: DG
authors.lastname: Patterson
authors.forename: Y Leon
authors.initials: YL
authors.lastname: Guo
mesh_terms: D000328:Adult; D000368:Aged; D001572:Benzofurans / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D001944:Breath Tests; D002110:Caffeine / Q000493:pharmacokinetics*; D002247:Carbon Isotopes / Q000032:analysis / Q000378:metabolism; D019388:Cytochrome P-450 CYP1A2 / Q000378:metabolism*; D000072338:Dibenzofurans, Polychlorinated; D004785:Environmental Pollutants / Q000097:blood*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011078:Polychlorinated Biphenyls / Q000097:blood*; D012907:Smoking / Q000378:metabolism
chemical_list: D001572:Benzofurans; D015415:Biomarkers; D002247:Carbon Isotopes; D000072338:Dibenzofurans, Polychlorinated; D004785:Environmental Pollutants; D002110:Caffeine; D011078:Polychlorinated Biphenyls; C504573:CYP1A2 protein, human; D019388:Cytochrome P-450 CYP1A2