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Pierre Ayotte,^1,2 Éric Dewailly,¹ George H. Lambert,³ Sherry L. Perkins,⁴ Raymond Poon,⁵ Mark Feeley,⁶ Christian Larochelle,¹ and Daria Pereg¹

¹Unité de Recherche en Santé Publique, Centre Hospitalier Universitaire de Québec, Université Laval, Québec, Canada; ²Laboratoire des Biomarqueurs, Institut National de Santé Publique du Québec, Québec, Canada; ³Environmental and Occupational Health Sciences Institute, Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey, Piscataway, New Jersey, USA; ⁴Division of Biochemistry, Ottawa Hospital, Ottawa, Ontario, Canada; ⁵Environmental Health Science Bureau, and ⁶Bureau of Chemical Safety, Health Canada, Ottawa, Ontario, Canada

Abstract
The Lower North Shore region of the St. Lawrence River is home to a fish-eating population that displays an unusually high body burden of several organochlorines, including polychlorinated biphenyls (PCBs) and dioxin-like compounds (DLCs) . We measured biomarkers indicative of liver enzyme induction and investigated the relationship with organochlorine body burden in adult volunteers from this population. We determined plasma concentrations of PCBs and chlorinated pesticides by high-resolution gas chromatography (HRGC) with electron capture detection. DLC concentrations were measured by the dioxin-receptor chemically activated luciferase expression (DR-CALUX) assay and in a subset of participants, by HRGC/high-resolution mass spectrometry. We measured cotinine, d-glucaric acid, and porphyrins in morning urine samples and determined liver CYP1A2 activity in vivo using the caffeine breath test. Neither DLC concentrations as measured by the DR-CALUX nor PCB-153 concentrations, the latter representing total PCB exposure, were correlated with biomarkers of effects. Smoking (morning urinary cotinine concentration) was positively related to CYP1A2 activity as measured by the caffeine breath test (p < 0.01) . Liver CYP1A2 activity was in turn negatively correlated with PCB-105:PCB-153 and PCB-118:PCB-153 congener ratios (p < 0.05) . Hence, despite the relatively high body burden of PCBs and DLCs in this population, only smoking had a significant correlation with biomarkers of hepatic enzyme induction. Our data are consistent with smoking-induced liver CYP1A2 activity altering heme metabolism and increasing the biotransformation of mono-ortho PCB congeners. Key words: cytochrome P450 CYP1A2, d-glucaric acid, dioxins, enzyme induction, food chain, organochlorine insecticides, polychlorinated biphenyls, porphyrins, smoking. Environ Health Perspect 113:1318-1324 (2005) . doi:10.1289/ehp.7970 available via http://dx.doi.org/ [Online 1 June 2005]

Address correspondence to P. Ayotte, Unité de Recherche en Santé Publique, Centre Hospitalier Universitaire de Québec, 945 Ave. Wolfe, Québec, QC, Canada G1V 5B3. Telephone: (418) 650-5115 ext. 4654. Fax: (418) 654-2148. E-mail: pierre.ayotte@inspq.qc.ca

Many thanks to J.-P. Weber, A. Leblanc, and É. Pelletier from the Laboratoire de Toxicologie of the Institut National de Santé Publique du Québec for performing organochlorine analyses.

This study was supported by Health Canada's Great Lakes Health Effects and St. Lawrence Vision 2000 Programs.

The authors declare they have no competing financial interests.

Received 27 January 2005 ; accepted 1 June 2005.