Literature DB >> 7757172

Induction of P-450 in workers exposed to dioxin.

W Halperin1, W Kalow, M H Sweeney, B K Tang, M Fingerhut, B Timpkins, K Wille.   

Abstract

OBJECTIVES: To examine the effects of occupational exposure to substances contaminated with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on cytochrome P-4501A2 activity in a cross sectional medical survey.
METHODS: The exposed workers had been employed at two chemical plants > 15 years earlier in the manufacture of 2,4, 5-trichlorophenol and its derivatives. The control group consisted of people with no occupational exposure to phenoxy herbicides and who lived within the communities of the exposed workers. A total of 58 workers and 125 unexposed controls participated in the analysis. Cytochrome P-450 activity was assessed with test that measures caffeine metabolites in the urine. A ratio of metabolites of caffeine (CMR) constituted a measure of P-4501A2 activity.
RESULTS: Compared with the control group in multivariate logistic regression, raised non-significant associations were found for three of four categories of TCDD in exposed workers (TCDD < 20 pg/g, odds ratio (OR) 1.7, 95% confidence interval (95% CI) 0.6 to 5.0, TCDD 20-66, OR 0.3, 95% CI 0.0 to 1.7; TCDD 67-147, OR 2.3, 95% CI 0.6 to 8.8; TCDD > or = 148, OR 3.1, 95% CI 0.8 to 12.5). We found a strongly significant association of CMR and urinary cotinine, a measure of smoking, and urinary free ethanol. We found weak non-significant associations between P-4501A2 activity and increased serum TCDD among workers.
CONCLUSIONS: The absence of an association between serum TCDD and cytochrome P-4501A2 may be due to the size of the study, insensitivity of the CMR to assess cytochrome P-4501A2 activity, or inadequate levels of exposure, although these were among the highest in human groups tested.

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Year:  1995        PMID: 7757172      PMCID: PMC1128160          DOI: 10.1136/oem.52.2.86

Source DB:  PubMed          Journal:  Occup Environ Med        ISSN: 1351-0711            Impact factor:   4.402


  21 in total

Review 1.  Enzyme induction in the cytochrome P-450 system.

Authors:  A B Okey
Journal:  Pharmacol Ther       Date:  1990       Impact factor: 12.310

2.  Human CYP1A2: sequence, gene structure, comparison with the mouse and rat orthologous gene, and differences in liver 1A2 mRNA expression.

Authors:  K Ikeya; A K Jaiswal; R A Owens; J E Jones; D W Nebert; S Kimura
Journal:  Mol Endocrinol       Date:  1989-09

3.  Chlorinated dibenzo-p-dioxins: potent inducers of delta-aminolevulinic acid synthetase and aryl hydrocarbon hydroxylase. II. A study of the structure-activity relationship.

Authors:  A Poland; E Glover
Journal:  Mol Pharmacol       Date:  1973-11       Impact factor: 4.436

Review 4.  Induction of drug-metabolizing enzymes: mechanisms and consequences.

Authors:  A B Okey; E A Roberts; P A Harper; M S Denison
Journal:  Clin Biochem       Date:  1986-04       Impact factor: 3.281

Review 5.  2,3,7,8-tetrachlorodibenzo-p-dioxin and related halogenated aromatic hydrocarbons: examination of the mechanism of toxicity.

Authors:  A Poland; J C Knutson
Journal:  Annu Rev Pharmacol Toxicol       Date:  1982       Impact factor: 13.820

Review 6.  Dioxins and the Ah receptor.

Authors:  E K Silbergeld; T A Gasiewicz
Journal:  Am J Ind Med       Date:  1989       Impact factor: 2.214

7.  A simple test for acetylator phenotype using caffeine.

Authors:  D M Grant; B K Tang; W Kalow
Journal:  Br J Clin Pharmacol       Date:  1984-04       Impact factor: 4.335

Review 8.  Genetic variation in the human hepatic cytochrome P-450 system.

Authors:  W Kalow
Journal:  Eur J Clin Pharmacol       Date:  1987       Impact factor: 2.953

9.  Cancer mortality in workers exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin.

Authors:  M A Fingerhut; W E Halperin; D A Marlow; L A Piacitelli; P A Honchar; M H Sweeney; A L Greife; P A Dill; K Steenland; A J Suruda
Journal:  N Engl J Med       Date:  1991-01-24       Impact factor: 91.245

10.  The caffeine breath test and caffeine urinary metabolite ratios in the Michigan cohort exposed to polybrominated biphenyls: a preliminary study.

Authors:  G H Lambert; D A Schoeller; H E Humphrey; A N Kotake; H Lietz; M Campbell; W Kalow; S P Spielberg; M Budd
Journal:  Environ Health Perspect       Date:  1990-11       Impact factor: 9.031

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  6 in total

1.  Induction of cytochrome P450 1A by cow milk-based formula: a comparative study between human milk and formula.

Authors:  Haibo Xu; Ratheishan Rajesan; Patricia Harper; Richard B Kim; Bo Lonnerdal; Mingdong Yang; Satoko Uematsu; Janine Hutson; Jo Watson-MacDonell; Shinya Ito
Journal:  Br J Pharmacol       Date:  2005-09       Impact factor: 8.739

Review 2.  Dioxin: a review of its environmental effects and its aryl hydrocarbon receptor biology.

Authors:  Prabir K Mandal
Journal:  J Comp Physiol B       Date:  2005-04-08       Impact factor: 2.200

3.  Caffeine N3-demethylation (CYP1A2) in a population with an increased exposure to polychlorinated biphenyls.

Authors:  Maria Skaalum Petersen; Jónrit Halling; Per Damkier; Flemming Nielsen; Philippe Grandjean; Pál Weihe; Kim Brøsen
Journal:  Eur J Clin Pharmacol       Date:  2006-11-07       Impact factor: 2.953

4.  Immunological markers among workers exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin.

Authors:  W Halperin; R Vogt; M H Sweeney; G Shopp; M Fingerhut; M Petersen
Journal:  Occup Environ Med       Date:  1998-11       Impact factor: 4.402

Review 5.  Animal models of human response to dioxins.

Authors:  J A Grassman; S A Masten; N J Walker; G W Lucier
Journal:  Environ Health Perspect       Date:  1998-04       Impact factor: 9.031

6.  PCB exposure and in vivo CYP1A2 activity among Native Americans.

Authors:  Edward F Fitzgerald; Syni-An Hwang; George Lambert; Marta Gomez; Alice Tarbell
Journal:  Environ Health Perspect       Date:  2005-03       Impact factor: 9.031

  6 in total

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