{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T14:34:16Z","timestamp":1786631656063,"version":"build-2736575974"},"reference-count":58,"publisher":"American Chemical Society (ACS)","issue":"3","license":[{"start":{"date-parts":[[2017,12,29]],"date-time":"2017-12-29T00:00:00Z","timestamp":1514505600000},"content-version":"vor","delay-in-days":4768,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2005,3,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Cytochrome P-450 1A2 (CYP1A2) is an enzyme involved in the metabolic activation of some carcinogens and is believed to be induced by xenobiotics. Very few studies, however, have investigated the association between environmental exposures and in vivo CYP1A2 activity in humans. To address this issue, a study was conducted of CYP1A2 activity among Native Americans exposed to polychlorinated biphenyls (PCBs) from the consumption of fish from the St. Lawrence River. At the Mohawk Nation at Akwesasne (in New York and in Ontario and Quebec, Canada), 103 adults were interviewed, and they donated blood for serum PCB analysis and underwent the caffeine breath test (CBT), a safe and noninvasive procedure that uses caffeine as a probe for CYP1A2 activity in vivo. The results supported the findings of other studies that CBT values are higher among smokers and men and lower among women who use oral contraceptives. Despite a relatively low average total PCB body burden in this population, the sum of serum levels for nine mono- or di-ortho-substituted PCB congeners showed positive associations with CBT values (p = 0.052 wet weight and p = 0.029 lipid adjusted), as did toxic equivalent quantities (TEQs; p = 0.091 for wet weight and 0.048 for lipid adjusted). Regarding individual congeners, serum levels of PCB-153, PCB-170, and PCB-180 were significantly correlated with CBT values. The results support the notion that CYP1A2 activity may be a marker of an early biological effect of exposure to PCBs in humans and that the CBT may be a useful tool to monitor such effects.<\/jats:p>","DOI":"10.1289\/ehp.7370","type":"journal-article","created":{"date-parts":[[2004,12,9]],"date-time":"2004-12-09T16:03:16Z","timestamp":1102608196000},"page":"272-277","source":"Crossref","is-referenced-by-count":29,"title":["PCB Exposure and\n                    <i>in Vivo<\/i>\n                    CYP1A2 Activity among Native Americans"],"prefix":"10.1021","volume":"113","author":[{"given":"Edward F.","family":"Fitzgerald","sequence":"first","affiliation":[{"name":"1University at Albany, School of Public Health, Rensselaer, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Syni-An","family":"Hwang","sequence":"additional","affiliation":[{"name":"2New York State Department of Health, Center for Environmental Health, Troy, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George","family":"Lambert","sequence":"additional","affiliation":[{"name":"3University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, New Brunswick, New Jersey, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Gomez","sequence":"additional","affiliation":[{"name":"2New York State Department of Health, Center for Environmental Health, Troy, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alice","family":"Tarbell","sequence":"additional","affiliation":[{"name":"4Akwesasne Task Force on the Environment, Mohawk Nation at Akwesasne, Hogansburg, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2004,12,9]]},"reference":[{"key":"2026080410152710900_micit1","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1007\/BF00544361","article-title":"Impairment of caffeine clearance by chronic use of low-dose oestrogen-containing oral contraceptives","volume":"28","author":"Abernethy","year":"1985","journal-title":"Eur J Clin Pharmacol"},{"key":"2026080410152710900_micit2","author":"ASTM"},{"key":"2026080410152710900_micit3","first-page":"555","article-title":"Glass capillary chromatography for sensitive, accurate polychlorinated biphenyl analysis","volume":"65","author":"Bush","year":"1982","journal-title":"J Assoc Offic Anal Chem"},{"key":"2026080410152710900_micit4","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1007\/BF01055530","article-title":"Polychlorinated biphenyl congeners (PCBs), p,p\u2032-DDE and hexachlorobenzene in human milk in three areas of upstate NY","volume":"14","author":"Bush","year":"1985","journal-title":"Arch Environ Contam Toxicol"},{"key":"2026080410152710900_micit5","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1007\/BF01056331","article-title":"Polychlorobiphenyl (PCB) congeners, p,p\u2032-DDE and hexachlorobenzene in maternal, and fetal cord blood from mothers in upstate NY","volume":"13","author":"Bush","year":"1984","journal-title":"Arch Environ Contam Toxicol"},{"key":"2026080410152710900_micit6","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1097\/00008571-199206000-00003","article-title":"Determination of CYP1A2 and NAT2 phenotypes in human populations by analysis of caffeine urinary metabolites","volume":"2","author":"Butler","year":"1992","journal-title":"Pharmacogenetics"},{"key":"2026080410152710900_micit7","first-page":"237","article-title":"Biotransformation of caffeine, paraxanthine, theophylline, and theobromine by polycyclic aromatic hydrocarbon-inducible cytochrome(s) P-450 in human liver microsomes","volume":"15","author":"Campbell","year":"1987","journal-title":"Am Soc Pharmacol Exp Ther"},{"key":"2026080410152710900_micit8","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1038\/clpt.1987.126","article-title":"A urinary metabolite ratio that reflects systemic caffeine clearance","volume":"42","author":"Campbell","year":"1987","journal-title":"Clin Pharmacol Ther"},{"key":"2026080410152710900_micit9","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1002\/cpt1976206633","article-title":"Enhanced phenacetin metabolism in human subjects fed charcoal-broiled beef","volume":"20","author":"Conney","year":"1976","journal-title":"Clin Pharmacol Ther"},{"key":"2026080410152710900_micit10","doi-asserted-by":"crossref","first-page":"606","DOI":"10.1002\/(SICI)1097-0274(199712)32:6<606::AID-AJIM6>3.0.CO;2-N","article-title":"Correlations among human blood levels of specific PCB congeners and implications for epidemiologic studies","volume":"32","author":"DeVoto","year":"1997","journal-title":"Am J Ind Med"},{"key":"2026080410152710900_micit11","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1097\/00008571-199510000-00001","article-title":"Role of cytochrome P4501A2 in chemical carcinogenesis: implications for human variability in expression and enzyme activity","volume":"5","author":"Eaton","year":"1995","journal-title":"Pharmacogenetics"},{"key":"2026080410152710900_micit12","author":"Ecology and Environment Inc"},{"key":"2026080410152710900_micit13","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1177\/074823379601200308","article-title":"Polychlorinated biphenyl (PCB) and dichloro-diphenyl dichloroethylene (DDE) exposure among Native American men from contaminated Great Lakes fish and wildlife","volume":"12","author":"Fitzgerald","year":"1996","journal-title":"Toxicol Ind Health"},{"key":"2026080410152710900_micit14","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1006\/enrs.1998.3908","article-title":"Local fish consumption and serum PCB concentrations among Mohawk men at Akwesasne","volume":"80","author":"Fitzgerald","year":"1999","journal-title":"Environ Res"},{"key":"2026080410152710900_micit15","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1016\/S0013-9351(03)00133-6","article-title":"Dietary, occupational, and residential exposure and serum PCB concentrations among Mohawk women at Akwesasne","volume":"94","author":"Fitzgerald","year":"2004","journal-title":"Environ Res"},{"key":"2026080410152710900_micit16","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1002\/jhrc.1240191202","article-title":"Complete PCB congener distributions for 17 Aroclor mixtures determined by 3 HRGC systems optimized for comprehensive, quantitative, congener-specific analysis","volume":"19","author":"Frame","year":"1996","journal-title":"J High Resol Chromatogr"},{"key":"2026080410152710900_micit17","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1002\/(SICI)1097-0274(199901)35:1<15::AID-AJIM3>3.0.CO;2-Z","article-title":"Correlations among polychlorinated biphenyls, dioxins, and furans in humans","volume":"35","author":"Gladen","year":"1999","journal-title":"Am J Ind Med"},{"key":"2026080410152710900_micit18","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1136\/oem.52.2.86","article-title":"Induction of P-450 in workers exposed to dioxin","volume":"52","author":"Halperin","year":"1995","journal-title":"Occup Environ Med"},{"key":"2026080410152710900_micit19","author":"Hansen"},{"key":"2026080410152710900_micit20","first-page":"529","article-title":"A study of gender-based cytochrome P4501A2 variability: a possible mechanism for the male excess of bladder cancer","volume":"4","author":"Horn","year":"1995","journal-title":"Cancer Epidemiol Biomarkers Prev"},{"key":"2026080410152710900_micit21","first-page":"98","article-title":"Detection of a novel cytochrome P-450 1A2 polymorphism (F21L) in Chinese","volume":"27","author":"Huang","year":"1999","journal-title":"Am Soc Pharmacol Exp Ther"},{"key":"2026080410152710900_micit22","doi-asserted-by":"crossref","first-page":"37","DOI":"10.3109\/03602539409029783","article-title":"Biochemical individuality and its implications for drug and carcinogen metabolism: recent insights from acetyltransferase and cytochrome P4501A2 phenotyping and genotyping in humans","volume":"16","author":"Kadlubar","year":"1994","journal-title":"Drug Metab Rev"},{"key":"2026080410152710900_micit23","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1038\/clpt.1991.8","article-title":"Caffeine as a metabolic probe: exploration of the enzyme-inducing effect of cigarette smoke","volume":"49","author":"Kalow","year":"1991","journal-title":"Clin Pharmacol Ther"},{"key":"2026080410152710900_micit24","doi-asserted-by":"crossref","first-page":"508","DOI":"10.1038\/clpt.1991.176","article-title":"Use of caffeine metabolite ratios to explore CYP1A2 and xanthine oxidase activities","volume":"50","author":"Kalow","year":"1991","journal-title":"Clin Pharmacol Ther"},{"key":"2026080410152710900_micit25","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1038\/clpt.1993.63","article-title":"The use of caffeine for enzyme assays: a critical appraisal","volume":"53","author":"Kalow","year":"1993","journal-title":"Clin Pharmacol Ther"},{"key":"2026080410152710900_micit26","first-page":"159","article-title":"CYP1A1","volume":"148","author":"Kawajiri","year":"1999","journal-title":"IARC Sci Publ"},{"key":"2026080410152710900_micit27","doi-asserted-by":"crossref","first-page":"1721","DOI":"10.1016\/0045-6535(94)90428-6","article-title":"PCB and dioxin levels in plasma and human milk of 418 Dutch women and their infants, predictive value of PCB congener levels in maternal plasma for fetal and infant\u2019s exposure to PCBs and dioxins","volume":"28","author":"Koopman-Esseboom","year":"1994","journal-title":"Chemosphere"},{"key":"2026080410152710900_micit28","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1038\/clpt.1982.157","article-title":"The caffeine CO2 breath test: dose response and route of N-demethylation in smokers and nonsmokers","volume":"32","author":"Kotake","year":"1982","journal-title":"Clin Pharmacol Ther"},{"key":"2026080410152710900_micit29","author":"Lacetti"},{"key":"2026080410152710900_micit30","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1006\/enrs.1998.3920","article-title":"Cytochrome P450 CYP1A1 enzyme activity and DNA adducts in placenta of women environmentally exposed to organochlorines","volume":"80","author":"Lagueux","year":"1999","journal-title":"Environ Res"},{"key":"2026080410152710900_micit31","doi-asserted-by":"crossref","first-page":"297","DOI":"10.3109\/00498259609046709","article-title":"Induction of cytochrome P450 isoenzymes in cultured precision-cut rat and human liver slices","volume":"26","author":"Lake","year":"1996","journal-title":"Xenobiotica"},{"key":"2026080410152710900_micit32","first-page":"119","article-title":"The CO2 breath tests as monitors of the cytochrome P450 dependent mixed function monooxygenase system","volume":"135","author":"Lambert","year":"1983","journal-title":"Dev Pharmacol"},{"key":"2026080410152710900_micit33","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1289\/ehp.9089175","article-title":"The caffeine breath test and caffeine urinary metabolite ratios in the Michigan cohort exposed to polybrominated biphenyls: a prelimary study","volume":"89","author":"Lambert","year":"1990","journal-title":"Environ Health Perspect"},{"key":"2026080410152710900_micit34","first-page":"173","article-title":"Human cytochrome P4501A2","volume":"148","author":"Landi","year":"1999","journal-title":"IARC Sci Publ"},{"key":"2026080410152710900_micit35","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1080\/00039890009603406","article-title":"Correlations among human plasma levels of dioxin-like compounds and polychlorinated biphenyls (PCBs) and implications for epidemiologic studies","volume":"55","author":"Longnecker","year":"2000","journal-title":"Arch Environ Health"},{"key":"2026080410152710900_micit36","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1289\/ehp.877679","article-title":"Placental markers of human exposure to polychlorinated biphenyls and polychlorinated dibenzo-furans","volume":"76","author":"Lucier","year":"1987","journal-title":"Environ Health Perspect"},{"key":"2026080410152710900_micit37","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1289\/ehp.8981225","article-title":"Environmental occurrence, abundance, and potential toxicity of PCB congeners: considerations for a congener-specific analysis","volume":"81","author":"McFarland","year":"1989","journal-title":"Environ Health Perspect"},{"key":"2026080410152710900_micit38","first-page":"413","article-title":"Phenotyping of CYP1A2 in Japanese population by analysis of caffeine urinary metabolites: absence of mutation prescribing the phenotype in the CYP1A2 gene","volume":"3","author":"Nakajima","year":"1994","journal-title":"Cancer Epidemiol Biomarkers Prev"},{"key":"2026080410152710900_micit39","author":"NYSDEC"},{"key":"2026080410152710900_micit40","author":"NYSDOH"},{"key":"2026080410152710900_micit41","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1002\/cpt197925188","article-title":"Stimulatory effect of brussels sprouts and cabbage on human drug metabolism","volume":"25","author":"Pantuck","year":"1979","journal-title":"Clin Pharmacol Ther"},{"key":"2026080410152710900_micit42","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1046\/j.1365-2125.1998.00684.x","article-title":"Induction of CYP1A2 activity by carbamazepine in children using the caffeine breath test","volume":"45","author":"Parker","year":"1998","journal-title":"Br J Clin Pharmacol"},{"key":"2026080410152710900_micit43","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/0009-2797(81)90059-4","article-title":"Poly-chlorinated biphenyls as inducers of hepatic microsomal enzymes: effects of di-ortho substitution","volume":"35","author":"Parkinson","year":"1981","journal-title":"Chem Biol Interact"},{"issue":"suppl 1","key":"2026080410152710900_micit44","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1289\/ehp.94102s1195","article-title":"Levels of non-ortho-subsituted (coplanar), mono- and di-ortho-substituted polychlorinated biphenyls, dibenzo-p-dioxins, and dibenzofurans in human serum and adipose tissue","volume":"102","author":"Patterson","year":"1994","journal-title":"Environ Health Perspect"},{"key":"2026080410152710900_micit45","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1007\/BF01055015","article-title":"Chlorinated hydrocarbon levels in human serum: effects of fasting and feeding","volume":"18","author":"Phillips","year":"1989","journal-title":"Arch Environ Contam Toxicol"},{"key":"2026080410152710900_micit46","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1007\/BF00548769","article-title":"Rapid onset of an increase in caffeine residence time in young women due to oral contraceptives","volume":"26","author":"Rietveld","year":"1984","journal-title":"Eur J Clin Pharmacol"},{"key":"2026080410152710900_micit47","author":"RMT"},{"key":"2026080410152710900_micit48","first-page":"1204","article-title":"Specific and dose-dependent enzyme induction by omeprazole in human beings","volume":"20","author":"Rost","year":"1994","journal-title":"Hepatology"},{"key":"2026080410152710900_micit49","author":"Rothman"},{"key":"2026080410152710900_micit50","doi-asserted-by":"crossref","first-page":"87","DOI":"10.3109\/10408449409049308","article-title":"Polychlorinated Biphenyls (PCBs): environmental impact, biochemical and toxic responses, and implications for risk assessment","volume":"24","author":"Safe","year":"1994","journal-title":"Crit Rev Toxicol"},{"key":"2026080410152710900_micit51","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1002\/bms.1200060809","article-title":"A microprocessor controlled mass spectrometer for the fully automated purification and isotopic analysis of breath carbon dioxide","volume":"6","author":"Schoeller","year":"1979","journal-title":"Biomed Mass Spectrom"},{"key":"2026080410152710900_micit52","author":"Skinner"},{"key":"2026080410152710900_micit53","author":"Sloan"},{"key":"2026080410152710900_micit54","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1289\/ehp.98106775","article-title":"Toxic equivalency factors (TEFs) for PCBs, PCDDs, PCDFs for humans and wildlife","volume":"106","author":"Van den Berg","year":"1998","journal-title":"Environ Health Perspect"},{"key":"2026080410152710900_micit55","doi-asserted-by":"crossref","first-page":"1561","DOI":"10.1093\/carcin\/13.9.1561","article-title":"Foreign compound metabolism capacity in man measured from metabolites of dietary caffeine","volume":"13","author":"Vistisen","year":"1992","journal-title":"Carcinogenesis"},{"key":"2026080410152710900_micit56","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1016\/0168-8278(95)80263-0","article-title":"The influence of rifampin treatment on caffeine clearance in healthy man","volume":"22","author":"Wietholtz","year":"1995","journal-title":"Hepatology"},{"key":"2026080410152710900_micit57","first-page":"141","article-title":"Environmental organochlorine exposure as a potential etiologic factor in breast cancer","volume":"103","author":"Wolff","year":"1995","journal-title":"Environ Health Perspect"},{"key":"2026080410152710900_micit58","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1093\/toxsci\/63.1.65","article-title":"Inducing effects of dioxin-like polychlorinated biphenyls on CYP1A in the human hepatoblastoma cell line HepG2, the rat hepatoma cell line H4IIE, and rat primary hepatocytes: comparison of relative potencies","volume":"63","author":"Zeiger","year":"2001","journal-title":"Toxicology"}],"container-title":["Environmental Health Perspectives"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/evhpaz\/article-pdf\/113\/3\/272\/66388333\/ehp.7370.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/evhpaz\/article-pdf\/113\/3\/272\/66388333\/ehp.7370.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T13:46:14Z","timestamp":1786628774000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/evhpaz\/article-lookup\/doi\/10.1289\/ehp.7370"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2004,12,9]]},"references-count":58,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2004,12,9]]},"published-print":{"date-parts":[[2005,3,1]]}},"URL":"https:\/\/doi.org\/10.1289\/ehp.7370","relation":{},"ISSN":["0091-6765","1552-9924"],"issn-type":[{"value":"0091-6765","type":"print"},{"value":"1552-9924","type":"electronic"}],"subject":[],"published":{"date-parts":[[2004,12,9]]}}}