Caffeine N3-demethylation (CYP1A2) in a Population with an Increased Exposure to Polychlorinated Biphenyls

Overview

Journal Eur J Clin Pharmacol

Specialty Pharmacology

Date 2006 Nov 8

PMID 17089110

Citations 12

Authors

Maria Skaalum Petersen

Jonrit Halling

Per Damkier

Flemming Nielsen

Philippe Grandjean

Pal Weihe

Kim Brosen

Affiliations

Soon will be listed here.

Abstract

Objective: To investigate the CYP1A2 phenotype distribution in a population with an increased exposure to polychlorinated biphenyls (PCBs) that would likely induce an increased activity of this enzyme. Further, to investigate the effect of sex, smoking, and oral contraceptive use on the CYP1A2 activity.

Methods: In 305 randomly selected Faroese residents aged 18-60 years, the CYP1A2 activity was determined following oral intake of a caffeine dose and subsequent determination of the urinary metabolites and calculation of the caffeine metabolic ratio (CMR). PCB exposure was assessed by measuring the serum concentration of major congeners.

Results: The CYP1A2 phenotype distribution was unimodal. The CMR was significantly higher both in smoking men and in smoking women, independent of oral contraceptive use, as compared with non-smokers. Among non-smokers, the CMR was significantly higher in women not using oral contraceptives than in those using oral contraceptives; a similar difference could not be established among smokers. The CMR appeared higher in men than in women, but stratified analyses confirmed a significant sex-related difference only among smokers not using oral contraceptives. Overall, the mean CMR in Faroese was significantly higher compared with the mean CMR in Danish historical controls. No association was found with PCB exposure and individual PCB congeners, except for one of three dioxin-like congeners, in confounder-adjusted multiple regression analyses.

Conclusion: The CYP1A2 phenotype in Faroese residents was unimodally distributed and showed the inducing effect of smoking and the inhibiting effect of use of oral contraceptives, but a sex-related difference was not apparent after confounder adjustment. There was no statistically significant association between CMR and PCB exposure.

Citing Articles

Concentrations of tetanus and diphtheria antibodies in vaccinated Greenlandic children aged 7-12 years exposed to marine pollutants, a cross sectional study.

Timmermann C, Pedersen H, Weihe P, Bjerregaard P, Nielsen F, Heilmann C Environ Res. 2021; 203:111712.

PMID: 34343554 PMC: 11061314. DOI: 10.1016/j.envres.2021.111712.

Joint and independent neurotoxic effects of early life exposures to a chemical mixture: A multi-pollutant approach combining ensemble learning and g-computation.

Oulhote Y, Coull B, Bind M, Debes F, Nielsen F, Tamayo I Environ Epidemiol. 2020; 3(5).

PMID: 32051926 PMC: 7015154. DOI: 10.1097/ee9.0000000000000063.

Environmental chemical exposures among Greenlandic children in relation to diet and residence.

Timmermann C, Pedersen H, Budtz-Jorgensen E, Bjerregaard P, Oulhote Y, Weihe P Int J Circumpolar Health. 2019; 78(1):1642090.

PMID: 31339476 PMC: 6711189. DOI: 10.1080/22423982.2019.1642090.

Reproductive Function in a Population of Young Faroese Men with Elevated Exposure to Polychlorinated Biphenyls (PCBs) and Perfluorinated Alkylate Substances (PFAS).

Petersen M, Halling J, Jorgensen N, Nielsen F, Grandjean P, Jensen T Int J Environ Res Public Health. 2018; 15(9).

PMID: 30200252 PMC: 6165232. DOI: 10.3390/ijerph15091880.

Secondary sex ratio in relation to exposures to polychlorinated biphenyls, dichlorodiphenyl dichloroethylene and methylmercury.

Timmermann C, Choi A, Petersen M, Nielsen F, Budtz-Jorgensen E, Weihe P Int J Circumpolar Health. 2017; 76(1):1406234.

PMID: 29195489 PMC: 5717715. DOI: 10.1080/22423982.2017.1406234.

References

Brosen K . Drug interactions and the cytochrome P450 system. The role of cytochrome P450 1A2. Clin Pharmacokinet. 1995; 29 Suppl 1:20-5. DOI: 10.2165/00003088-199500291-00005. View

Shimada T, Inoue K, Suzuki Y, Kawai T, Azuma E, Nakajima T . Arylhydrocarbon receptor-dependent induction of liver and lung cytochromes P450 1A1, 1A2, and 1B1 by polycyclic aromatic hydrocarbons and polychlorinated biphenyls in genetically engineered C57BL/6J mice. Carcinogenesis. 2002; 23(7):1199-207. DOI: 10.1093/carcin/23.7.1199. View

CAMPBELL M, Spielberg S, KALOW W . A urinary metabolite ratio that reflects systemic caffeine clearance. Clin Pharmacol Ther. 1987; 42(2):157-65. DOI: 10.1038/clpt.1987.126. View

Rasmussen B, Brosen K . Determination of urinary metabolites of caffeine for the assessment of cytochrome P4501A2, xanthine oxidase, and N-acetyltransferase activity in humans. Ther Drug Monit. 1996; 18(3):254-62. DOI: 10.1097/00007691-199606000-00006. View

Grandjean P, Weihe P, Burse V, Needham L, Heinzow B, Debes F . Neurobehavioral deficits associated with PCB in 7-year-old children prenatally exposed to seafood neurotoxicants. Neurotoxicol Teratol. 2001; 23(4):305-17. DOI: 10.1016/s0892-0362(01)00155-6. View

Lambert G, Schoeller D, Humphrey H, Kotake A, LIETZ H, Campbell M . The caffeine breath test and caffeine urinary metabolite ratios in the Michigan cohort exposed to polybrominated biphenyls: a preliminary study. Environ Health Perspect. 1990; 89:175-81. PMC: 1567793. DOI: 10.1289/ehp.9089175. View

Schrenk D, Brockmeier D, Morike K, Bock K, Eichelbaum M . A distribution study of CYP1A2 phenotypes among smokers and non-smokers in a cohort of healthy Caucasian volunteers. Eur J Clin Pharmacol. 1998; 53(5):361-7. DOI: 10.1007/s002280050394. View

Shimada T, Iwasaki M, Martin M, Guengerich F . Human liver microsomal cytochrome P-450 enzymes involved in the bioactivation of procarcinogens detected by umu gene response in Salmonella typhimurium TA 1535/pSK1002. Cancer Res. 1989; 49(12):3218-28. View

Nakajima M, Yokoi T, Mizutani M, Kinoshita M, Funayama M, Kamataki T . Genetic polymorphism in the 5'-flanking region of human CYP1A2 gene: effect on the CYP1A2 inducibility in humans. J Biochem. 1999; 125(4):803-8. DOI: 10.1093/oxfordjournals.jbchem.a022352. View

10.

Halperin W, KALOW W, Sweeney M, Tang B, Fingerhut M, Timpkins B . Induction of P-450 in workers exposed to dioxin. Occup Environ Med. 1995; 52(2):86-91. PMC: 1128160. DOI: 10.1136/oem.52.2.86. View

11.

Pavanello S, Pulliero A, Lupi S, Gregorio P, Clonfero E . Influence of the genetic polymorphism in the 5'-noncoding region of the CYP1A2 gene on CYP1A2 phenotype and urinary mutagenicity in smokers. Mutat Res. 2005; 587(1-2):59-66. DOI: 10.1016/j.mrgentox.2005.08.008. View

12.

Heilmann C, Grandjean P, Weihe P, Nielsen F, Budtz-Jorgensen E . Reduced antibody responses to vaccinations in children exposed to polychlorinated biphenyls. PLoS Med. 2006; 3(8):e311. PMC: 1551916. DOI: 10.1371/journal.pmed.0030311. View

13.

Huang J, Guo W, Lai M, Guo Y, Lambert G . Detection of a novel cytochrome P-450 1A2 polymorphism (F21L) in Chinese. Drug Metab Dispos. 1999; 27(1):98-101. View

14.

Aklillu E, Carrillo J, Makonnen E, Hellman K, Pitarque M, Bertilsson L . Genetic polymorphism of CYP1A2 in Ethiopians affecting induction and expression: characterization of novel haplotypes with single-nucleotide polymorphisms in intron 1. Mol Pharmacol. 2003; 64(3):659-69. DOI: 10.1124/mol.64.3.659. View

15.

Frye R, Matzke G, Adedoyin A, Porter J, Branch R . Validation of the five-drug "Pittsburgh cocktail" approach for assessment of selective regulation of drug-metabolizing enzymes. Clin Pharmacol Ther. 1997; 62(4):365-76. DOI: 10.1016/S0009-9236(97)90114-4. View

16.

Longnecker M, Wolff M, Gladen B, Brock J, Grandjean P, Jacobson J . Comparison of polychlorinated biphenyl levels across studies of human neurodevelopment. Environ Health Perspect. 2003; 111(1):65-70. PMC: 1241307. DOI: 10.1289/ehp.5463. View

17.

Fitzgerald E, Hwang S, Lambert G, Gomez M, Tarbell A . PCB exposure and in vivo CYP1A2 activity among Native Americans. Environ Health Perspect. 2005; 113(3):272-7. PMC: 1253751. DOI: 10.1289/ehp.7370. View

18.

Notarianni L, Oliver S, Dobrocky P, Bennett P, Silverman B . Caffeine as a metabolic probe: a comparison of the metabolic ratios used to assess CYP1A2 activity. Br J Clin Pharmacol. 1995; 39(1):65-9. PMC: 1364983. DOI: 10.1111/j.1365-2125.1995.tb04411.x. View

19.

Parsons W, NEIMS A . Effect of smoking on caffeine clearance. Clin Pharmacol Ther. 1978; 24(1):40-5. DOI: 10.1002/cpt197824140. View

20.

Rietveld E, Broekman M, Houben J, Eskes T, van Rossum J . Rapid onset of an increase in caffeine residence time in young women due to oral contraceptive steroids. Eur J Clin Pharmacol. 1984; 26(3):371-3. DOI: 10.1007/BF00548769. View