Impact of dioxins on antipyrine metabolism in firefighters

Chernyak, Yu. I.; Merinova, Alla P.; Shelepchikov, A. A.; Kolesnikov, S. I.; Grassman, Jean

doi:10.1016/j.toxlet.2016.04.006

Cited by 8 publications

(2 citation statements)

References 32 publications

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“…Positive correlations between the sum of the serum levels of nine PCB congeners and the caffeine breath test were demonstrated, and serum levels of three PCBs were significantly correlated with caffeine breath test values. Chernyak et al more recently demonstrated that firefighters exposed to dioxin had increased concentrations of 3‐hydroxymethylantipyrine, a metabolite of antipyrine used as a surrogate marker of CYP1A2 induction . Interestingly, Abraham et al compared CYP1A2 activities in two women highly exposed to TCDD and one man moderately exposed with those of 50 control subjects .…”

Section: Discussionmentioning

confidence: 99%

“…Chernyak et al more recently demonstrated that firefighters exposed to dioxin had increased concentrations of 3-hydroxymethylantipyrine, a metabolite of antipyrine used as a surrogate marker of CYP1A2 induction. 31 Interestingly, Abraham et al compared CYP1A2 activities in two women highly exposed to TCDD and one man moderately exposed with those of 50 control subjects. 19 Three methods were used to assess CYP1A2 activity ( 13 C breath test, total clearance and serum and urine metabolic ratio (UMR) of caffeine and metabolites).…”

Section: Discussionmentioning

confidence: 99%

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Cytochrome P450 1A2 activity and incidence of thyroid disease and cancer after chronic or acute exposure to dioxins

Samer

Gloor

Rollason

et al. 2019

Basic Clin Pharma Tox

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Background Dioxin (2,3,7,8‐tetrachlorodibenzo‐p‐dioxin; TCDD) is the most toxic congener of a family of structurally and mechanistically related persistent organic pollutants whose effects are mediated through the aryl hydrocarbon receptor (AhR). Induction of CYP1A1/2 by TCDD through the AhR depends on the magnitude and the duration of exposure. We aimed to assess CYP1A2 activity after acute and chronic exposure to TCDD. The Maincy cohort is a sample population from Melun in the Val‐de‐Seine region in France that lived for at least 5 years close to a waste incinerator emitting polluted vapours (1974‐2002) with high concentrations of dioxins (up to 2000 times the maximal recommended values). Acute exposure to TCDD (Viktor Yushchenko) has been described elsewhere by Sorg et al (Toxicol. Sci. 2012; 125:310‐317). Both are rare cases of well‐identified source of chronic and acute exposure to TCDD. Methods All subjects underwent a full medical history and physical examination and had a cutaneous examination, and a retro‐auricular skin biopsy was taken. A questionnaire was designed and used regarding demographic, personal, environmental and occupational characteristics. CYP1A2 activity was assessed 2 hours after the ingestion of a drink containing caffeine through measurement of the metabolic ratio of paraxanthine (17X) over caffeine (137X) by LC‐MS/MS or LC‐UV. CYP1A1 expression in skin biopsies was determined by immunohistochemical analysis. Results Forty‐seven exposed subjects (age 11‐78) and 31 controls were included in the study. Eleven exposed subjects had a history of thyroid disease (23.4%), and 7 (14.8%) had a cancer vs none and 1, respectively, in controls. Nodular skin lesions were found in 13 exposed subjects (27.7%) vs none in controls. Mean CYP1A2 activity of the exposed population was modestly elevated as compared to controls (17X/137X metabolic ratio of 0.475 vs 0.374, P = .051). CYP1A2 was, however, induced (17X/137X, metabolic ratio >0.5) in 27.6% of the exposed cases vs 6.4% of the controls. In contrast, acute dioxin exposure was associated with a strong induction (mean 17X/137X, metabolic ratio of 1.9) still present 29 months after the acute exposure. CYP1A1 was expressed in 59.6% of the skin biopsies (highly expressed in 31.9%) of the Maincy cohort. No correlation between CYP1A2 activity, CYP1A1 expression and clinical manifestations (thyroid disease, cancer, skin lesions) could be demonstrated. Conclusion Higher frequencies of dysthyroidism and cancer were detected in the population exposed chronically to dioxins from a waste incinerator. CYP1A2 was induced in 27.6% of the exposed population, while the magnitude of induction was fourfold higher after acute exposure in the case of Yushchenko.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Cytochrome P450 1A2 activity and incidence of thyroid disease and cancer after chronic or acute exposure to dioxins

Samer

Gloor

Rollason

et al. 2019

Basic Clin Pharma Tox

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Inhibition and induction of CYP enzymes in humans: an update

et al. 2020

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The cytochrome P450 (CYP) enzyme family is the most important enzyme system catalyzing the phase 1 metabolism of pharmaceuticals and other xenobiotics such as herbal remedies and toxic compounds in the environment. The inhibition and induction of CYPs are major mechanisms causing pharmacokinetic drug–drug interactions. This review presents a comprehensive update on the inhibitors and inducers of the specific CYP enzymes in humans. The focus is on the more recent human in vitro and in vivo findings since the publication of our previous review on this topic in 2008. In addition to the general presentation of inhibitory drugs and inducers of human CYP enzymes by drugs, herbal remedies, and toxic compounds, an in-depth view on tyrosine-kinase inhibitors and antiretroviral HIV medications as victims and perpetrators of drug–drug interactions is provided as examples of the current trends in the field. Also, a concise overview of the mechanisms of CYP induction is presented to aid the understanding of the induction phenomena.

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CYP3A Polymorphism and Chronic Mercury Intoxication

Chernyak

Merinova

2020

Bull Exp Biol Med

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Impact of dioxins on antipyrine metabolism in firefighters

Cited by 8 publications

References 32 publications

Cytochrome P450 1A2 activity and incidence of thyroid disease and cancer after chronic or acute exposure to dioxins

Cytochrome P450 1A2 activity and incidence of thyroid disease and cancer after chronic or acute exposure to dioxins

Inhibition and induction of CYP enzymes in humans: an update

CYP3A Polymorphism and Chronic Mercury Intoxication

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