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