The cytochrome P-450 isoenzyme CYP2E1 in the biological processing of industrial chemicals: consequences for occupational and environmental medicine

Bolt, Hermann M.; Roos, Peter H.; Thier, Ricarda

doi:10.1007/s00420-002-0407-4

Cited by 181 publications

(72 citation statements)

References 75 publications

(60 reference statements)

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“…The significantly lower HbGA:HbAA ratios and HbGA formation rate (per unit increase of HbAA) in non-Hispanic blacks may indicate differences in polymorphisms of the genes for CYP2E1 or of the genes for glutathione S -transferase (GST), which are involved in phase II detoxification of acrylamide and glycidamide. Different frequencies in polymorphisms in the genes for CYP2E1 in different race/ethnicity groups have been mentioned in literature (Bartsch et al 2000; Bolt et al 2003), and associations between polymorphisms in the genes for GST and the HbGA:HbAA ratio have been reported (Duale et al 2009). Medications and alcohol are also metabolized by CYP2E1 and thus may affect CYP2E1 activity and metabolism of acrylamide to glycidamide.…”

Section: Discussionmentioning

confidence: 99%

Exposure of the U.S. Population to Acrylamide in the National Health and Nutrition Examination Survey 2003–2004

Vesper

Caudill

Osterloh

et al. 2010

Environ Health Perspect

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BackgroundThe lifelong exposure of the population to acrylamide has raised concerns about the possible health effects of the chemical. Data on the extent of exposure to acrylamide and its primary metabolite, glycidamide, are needed to aid in the assessment of potential health effects.ObjectivesThe aim of this study was to assess human exposure to acrylamide and glycidamide in the general U.S. population through the measurement of hemoglobin adducts of acrylamide (HbAA) and glycidamide (HbGA).MethodsHbAA and HbGA were measured in 7,166 subjects from the National Health and Nutrition Examination Survey. Stratified HbAA and HbGA data were reported by sex, age groups, race/ethnicity (Mexican American, non-Hispanic black, non-Hispanic white), and smoking status based on serum cotinine levels. Covariate-adjusted geometric means for each demographic group were calculated using multiple regression analysis.ResultsHbAA and HbGA levels ranged from 3 to 910 and from 4 to 756 pmol/g hemoglobin, respectively, with smokers having the highest levels overall. Tobacco smoke exposure in nonsmokers had a small but significant effect on HbAA and HbGA levels. Adjusted geometric mean levels for children 3–11 years of age were higher than for adults ≥ 60 years of age [mean (95% confidence interval): HbAA, 54.5 (49.1–51.5) and HbGA, 73.9 (71.3–76.6) vs. HbAA, 46.2 (44.3–48.2) and HbGA, 41.8 (38.7–45.2)]. Levels were highest in Mexican Americans [HbAA: 54.8 (51.9–57.8), HbGA: 57.9 (53.7–62.5)], whereas non-Hispanic blacks had the lowest HbGA levels [43.5 (41.1–45.9)].ConclusionsU.S. population levels of acrylamide and glycidamide adducts are described. The high variability among individuals but modest differences between population subgroups suggest that sex, age, and race/ethnicity do not strongly affect acrylamide exposure. Adduct concentration data can be used to estimate relative exposure and to validate intake estimates.

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Section: Discussionmentioning

confidence: 99%

Exposure of the U.S. Population to Acrylamide in the National Health and Nutrition Examination Survey 2003–2004

Vesper

Caudill

Osterloh

et al. 2010

Environ Health Perspect

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“…carbon tetrachloride, benzene, nitrosamines, acetaminophen, halothane. Toxicity of these agents is enhanced in alcoholics (55,57–59). …”

Section: Alcohol-drug Interactionsmentioning

confidence: 99%

Alcohol Metabolism

Cederbaum

2012

Clinics in Liver Disease

891

713

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“…CYP2E1 metabolizes a variety of small, hydrophobic substrates including solvents such as chloroform and carbon tetrachloride, aromatic hydrocarbons such as benzene and toluene, alcohols such as ethanol and pentanol, aldehydes such as acetaldehyde, halogenated anesthetics such as enflurane and halothane, nitrosamines such as N,N-dimethylnitrosamine, and drugs such as chlorzoxazone and acetaminophen [35–41]. From a toxicological point of view, interest in CYP2E1 revolves around the ability of this P450 to metabolize and activate many toxicologically important compounds such as ethanol, carbon tetrachloride, acetaminophen, benzene, halothane, and many other halogenated substrates.…”

Section: Cyp2e1mentioning

confidence: 99%

CYP2E1 Sensitizes the Liver to LPS- and TNFα-Induced Toxicity via Elevated Oxidative and Nitrosative Stress and Activation of ASK-1 and JNK Mitogen-Activated Kinases

Cederbaum

Yang

Wang

et al. 2012

International Journal of Hepatology

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The mechanisms by which alcohol causes cell injury are not clear. A major mechanism is the role of lipid peroxidation and oxidative stress in alcohol toxicity. Many pathways have been suggested to play a role in how alcohol induces oxidative stress. Considerable attention has been given to alcohol elevated production of lipopolysaccharide (LPS) and TNFα and to alcohol induction of CYP2E1. These two pathways are not exclusive of each other; however, interactions between them, have not been extensively evaluated. Increased oxidative stress from induction of CYP2E1 sensitizes hepatocytes to LPS and TNFα toxicity and oxidants, activation of inducible nitric oxide synthase and p38 and JNK MAP kinases, and mitochondrial dysfunction are downstream mediators of this CYP2E1-LPS/TNFα-potentiated hepatotoxicity. This paper will summarize studies showing potentiated interactions between these two risk factors in promoting liver injury and the mechanisms involved including activation of the mitogen-activated kinase kinase kinase ASK-1. Decreasing either cytosolic or mitochondrial thioredoxin in HepG2 cells expressing CYP2E1 causes loss of cell viability and elevated oxidative stress via an ASK-1/JNK-dependent mechanism. We hypothesize that similar interactions occur as a result of ethanol induction of CYP2E1 and TNFα.

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The cytochrome P-450 isoenzyme CYP2E1 in the biological processing of industrial chemicals: consequences for occupational and environmental medicine

Cited by 181 publications

References 75 publications

Exposure of the U.S. Population to Acrylamide in the National Health and Nutrition Examination Survey 2003–2004

Exposure of the U.S. Population to Acrylamide in the National Health and Nutrition Examination Survey 2003–2004

Alcohol Metabolism

CYP2E1 Sensitizes the Liver to LPS- and TNFα-Induced Toxicity via Elevated Oxidative and Nitrosative Stress and Activation of ASK-1 and JNK Mitogen-Activated Kinases

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