title: PCB exposure and in vivo CYP1A2 activity among Native Americans.
abstract: 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.
authors.affiliation: University at Albany, School of Public Health, Rensselaer, New York, USA. eff02@health.state.ny.us
authors.forename: Edward F
authors.initials: EF
authors.lastname: Fitzgerald
authors.forename: Syni-An
authors.initials: SA
authors.lastname: Hwang
authors.forename: George
authors.initials: G
authors.lastname: Lambert
authors.forename: Marta
authors.initials: M
authors.lastname: Gomez
authors.forename: Alice
authors.initials: A
authors.lastname: Tarbell
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D015415:Biomarkers / Q000032:analysis; D003430:Cross-Sectional Studies; D019388:Cytochrome P-450 CYP1A2 / Q000494:pharmacology*; D004781:Environmental Exposure; D004785:Environmental Pollutants / Q000506:poisoning*; D005260:Female; D005399:Fishes; D005506:Food Contamination; D006801:Humans; D007198:Indians, North American; D008297:Male; D008875:Middle Aged; D009518:New York; D009864:Ontario; D011078:Polychlorinated Biphenyls / Q000097:blood / Q000506:poisoning*; D011247:Pregnancy; D011792:Quebec; D017747:Seafood; D012737:Sex Factors
chemical_list: D015415:Biomarkers; D004785:Environmental Pollutants; D011078:Polychlorinated Biphenyls; D019388:Cytochrome P-450 CYP1A2
references.citation: Arch Environ Health. 2000 May-Jun;55(3):195-200
references.pmid: 10908103
references.citation: IARC Sci Publ. 1999;(148):173-95
references.pmid: 10493258
references.citation: Environ Res. 2004 Feb;94(2):160-70
references.pmid: 14757379
references.citation: Clin Pharmacol Ther. 1976 Dec;20(6):633-42
references.pmid: 991534
references.citation: Clin Pharmacol Ther. 1979 Jan;25(1):88-95
references.pmid: 758247
references.citation: Biomed Mass Spectrom. 1979 Aug;6(8):350-5
references.pmid: 497361
references.citation: Chem Biol Interact. 1981 Apr;35(1):1-12
references.pmid: 6781768
references.citation: Clin Pharmacol Ther. 1982 Aug;32(2):261-9
references.pmid: 6807598
references.citation: Prog Clin Biol Res. 1983;135:119-45
references.pmid: 6420801
references.citation: Eur J Clin Pharmacol. 1984;26(3):371-3
references.pmid: 6734698
references.citation: Arch Environ Contam Toxicol. 1984 Sep;13(5):517-27
references.pmid: 6435547
references.citation: Eur J Clin Pharmacol. 1985;28(4):425-8
references.pmid: 4029248
references.citation: Arch Environ Contam Toxicol. 1985 Jul;14(4):443-50
references.pmid: 3929701
references.citation: Drug Metab Dispos. 1987 Mar-Apr;15(2):237-49
references.pmid: 2882985
references.citation: Clin Pharmacol Ther. 1987 Aug;42(2):157-65
references.pmid: 3608349
references.citation: Environ Health Perspect. 1987 Dec;76:79-87
references.pmid: 2834196
references.citation: Environ Health Perspect. 1989 May;81:225-39
references.pmid: 2503374
references.citation: Arch Environ Contam Toxicol. 1989 Jul-Aug;18(4):495-500
references.pmid: 2505694
references.citation: Clin Pharmacol Ther. 1991 Jan;49(1):44-8
references.pmid: 1988240
references.citation: Environ Health Perspect. 1990 Nov;89:175-81
references.pmid: 1965165
references.citation: Clin Pharmacol Ther. 1991 Nov;50(5 Pt 1):508-19
references.pmid: 1934864
references.citation: Carcinogenesis. 1992 Sep;13(9):1561-8
references.pmid: 1394840
references.citation: Clin Pharmacol Ther. 1993 May;53(5):503-14
references.pmid: 8491061
references.citation: Pharmacogenetics. 1992 Jun;2(3):116-27
references.pmid: 1306111
references.citation: Environ Health Perspect. 1994 Jan;102 Suppl 1:195-204
references.pmid: 8187709
references.citation: Crit Rev Toxicol. 1994;24(2):87-149
references.pmid: 8037844
references.citation: Drug Metab Rev. 1994;26(1-2):37-46
references.pmid: 8082575
references.citation: Cancer Epidemiol Biomarkers Prev. 1994 Jul-Aug;3(5):413-21
references.pmid: 7920209
references.citation: Hepatology. 1994 Nov;20(5):1204-12
references.pmid: 7927253
references.citation: J Hepatol. 1995 Jan;22(1):78-81
references.pmid: 7751591
references.citation: Occup Environ Med. 1995 Feb;52(2):86-91
references.pmid: 7757172
references.citation: Cancer Epidemiol Biomarkers Prev. 1995 Jul-Aug;4(5):529-33
references.pmid: 7549810
references.citation: Pharmacogenetics. 1995 Oct;5(5):259-74
references.pmid: 8563766
references.citation: Environ Health Perspect. 1995 Oct;103 Suppl 7:141-5
references.pmid: 8593861
references.citation: Xenobiotica. 1996 Mar;26(3):297-306
references.pmid: 8730921
references.citation: Toxicol Ind Health. 1996 May-Aug;12(3-4):361-8
references.pmid: 8843553
references.citation: Am J Ind Med. 1997 Dec;32(6):606-13
references.pmid: 9358917
references.citation: Br J Clin Pharmacol. 1998 Feb;45(2):176-8
references.pmid: 9491835
references.citation: Environ Health Perspect. 1998 Dec;106(12):775-92
references.pmid: 9831538
references.citation: Am J Ind Med. 1999 Jan;35(1):15-20
references.pmid: 9884741
references.citation: Drug Metab Dispos. 1999 Jan;27(1):98-101
references.pmid: 9884316
references.citation: Environ Res. 1999 Feb;80(2 Pt 2):S97-S103
references.pmid: 10092423
references.citation: Environ Res. 1999 May;80(4):369-82
references.pmid: 10330311
references.citation: IARC Sci Publ. 1999;(148):159-72
references.pmid: 10493257
references.citation: Toxicol Sci. 2001 Sep;63(1):65-73
references.pmid: 11509745