Abstract.
The importance of the isoform CYP2E1 of the human cytochrome P-450 superfamily of enzymes for occupational and environmental medicine is derived from its unique substrate spectrum that includes a number of highly important high-production chemicals, such as aliphatic and aromatic hydrocarbons, solvents and industrial monomers (i.a. alkanes, alkenes, aromatic and halogenated hydrocarbons). Many polymorphic genes, such as CYP2E1, show considerable differences in allelic distribution between different human populations. The polymorphic nature of the human CYP2E1 gene is significant for inter-individual differences in toxicity of its substrates. Since the substrate spectrum of CYP2E1 includes many compounds of basic relevance to industrial toxicology, a rationale for metabolic interactions of different CYP2E1 substrates is provided. In-depth research into the inter-individual phenotypic differences of human CYP2E1 enzyme activities was enabled by the recognition that the 6-hydroxylation of the drug chlorzoxazone is mediated by CYP2E1. Studies on CYP2E1 phenotyping have pointed to inter-individual variations in enzyme activities. There are consistent ethnic differences in CYP2E1 enzyme expression, mostly demonstrated between European and Japanese populations, which point to a major impact of genetic factors. The most frequently studied genetic polymorphisms are the restriction fragment length polymorphisms PstI/RsaI (mutant allele: CYP2E1*5B) located in the 5'-flanking region of the gene, as well as the DraI polymorphism (mutant allele: CYP2E1*6) located in intron 6. These polymorphisms are partly related, as they form the common allele designated CYP2E1*5A. Striking inter-ethnic differences between Europeans and Asians appear with respect to the frequencies of the CYP2E1*5A allele (only approximately 5% of Europeans are heterozygous, but 37% of Asians are, whilst 6% of Asians are homozygous). Available studies indicate a wide variation in human CYP2E1 expression, which are very likely based on complex gene–environment interactions. Major inter-ethnic differences are apparent on the genotyping and the phenotyping levels. Selected cases are presented where inter-ethnic variations of CYP2E1 may provide likely explanations for unexplained findings concerning industrial chemicals that are CYP2E1 substrates. Possible consequences of differential inter-individual and inter-ethnic susceptibilities are related to individual expressions of clinical symptoms of chemical toxicity, to results of biological monitoring of exposed workers, and to the interpretation of results of epidemiological or molecular-epidemiological studies.
Similar content being viewed by others
Notes
The current international nomenclature distinguishes the gene level from the protein/enzyme level by typing genes and gene variants in italics (CYP2E1 and its variant alleles, as opposed to CYP2E1 for the protein and associated enzyme activity). This is used throughout this review.
References
Appel KE, Peter H, Bolt HM (1981) Effect of potential antidotes on the acute toxicity of acrylonitrile. Int Arch Occup Environ Health 49:157–163
Bogaards JJP, van Immen B, van Bladeren PJ (1993) Interindividual differences in the in vitro conjugation of methylene chloride with glutathione S-transferase in 22 human liver samples. Biochem Pharmacol 45:2166–2169
Botto F, Seree E, el Khayari S, de Sousa G, Massacrier A, Placidi M, Cau P, Pellet W, Rahmani R, Barra Y (1994) Tissue-specific expression and methylation of the human CYP2E1 gene. Biochem Pharmacol 48:1095–1103
Brockmöller J, Cascorbi I, Kerb R, Roots I (1996) Combined analysis of inherited polymorphisms in arylamine N-acetyltransferase 2, glutathione S-transferases M1 and T1, microsomal epoxide hydrolase, and cytochrome P450 enzymes as modulators of bladder cancer risk. Cancer Res 56:3915–3925
Brüning T, Bolt HM (2000) Renal toxicity and carcinogenicity of trichloroethylene: key results, mechanisms, and controversies. Crit Rev Toxicol 30:253–285
Brüning T, Lammert M, Kempkes M, Thier R, Golka K, Bolt HM (1997) Influence of polymorphisms of GSTM1 and GSTT1 for risk of renal cell cancer in workers with a long-term and high exposure to trichloroethylene. Arch Toxicol 71:596–599
Burka LT, Sanchez IM, Ahmed AE, Ghanayem BI (1994) Comparative metabolism and disposition of acrylonitrile and methacrylonitrile in rats. Arch Toxicol 68:611–618
Carrière V, Berthou F, Baird S, Belloc C, Beaune P, de Waziers I (1996) Human cytochrome P450 2E1 (CYP2E1): from genotype to phenotype. Pharmacogenetics 6:203–211
Chen Y, Chen C, Jin SX, Zhou L (1999) The diagnosis and treatment of acute acrylonitrile poisoning: a clinical study of 144 cases. J Occup Health 41:172–176
Crosbie SJ, Blain PG, Williams FM (1997) Metabolism of n-hexane by rat liver and extrahepatic tissues and the effect of cytochrome P-450 inducers. Hum Exp Toxicol 16:131–137
DFG (1994) Addendum n-Hexan. In: Arbeitsmedizinisch-toxikologische Begründungen von BAT-Werten (n-Hexan (eds) Lehnert G, Henschler D. Wiley-VCH, Weinheim, Germany, pp 15–19)
DFG (1998) List of MAK and BAT values 1998. Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area, report no. 34. Wiley-VCH, Weinheim, Germany
DFG (2001) Biological monitoring. Heutige und künftige Möglichkeiten in der Arbeits- und Umweltmedizin. Wiley-VCH, Weinheim, Germany
Ding YP (1978) Chronic effects of acrylonitrile on eyes. J Ocul Inj Occup Ocul Dis (China) 9:19 ff
Dong ZG, Hong JY, Ma QA, Li DC, Bullock J, Gonzalez FJ, Park SS, Gelboin HV, Yang CS (1988) Mechanism of induction of cytochrome P-450ac (P-450j) in chemically induced and spontaneously diabetic rats. Arch Biochem Biophys 263:29–35
El Masri HA, Bell DA, Portier CJ (1999) Effects of glutathione transferase theta polymorphism on the risk estimates of dichloromethane to humans. Toxicol Appl Pharmacol 158:221–230
Fairbrother A, Grove J, de Waziers I, Steimel DT, Day CD, Crespi CL, Daly AK (1998) Detection and characterization of novel polymorphisms in the CYP2E1 gene. Pharmacogenetics 8:543–552
Fennell TR, Kedderis GL, Sumner CJ (1991) Urinary metabolites of 1,2,3-(13C)-acrylonitrile in rats and mice detected by 13C nuclear magnetic resonance spectroscopy. Chem Res Toxicol 4:678–687
Fong SW, Zhang RP, Chen YQ (1999) Progress on clinical study of acute acrylonitrile intoxication. Chin Occup Med 26:1–10
Fritsche E, Pittman GS, Bell DA (2000) Localization, sequence analysis, and ethnic distribution of a 96-bp insertion in the promoter of the human CYP2E1 gene. Mutat Res Genomics 432:1–5
Garte S, Crosti F (1999) A nomenclature system for metabolic gene polymorphisms. IARC Sci Publ 148:149–157
Garte S, Gaspari L, Alexandrie AK, Ambrosone C, Autrup H, Autrup JL, Baranova H, Bathum L, Benhamou S, Boffetta P, Bouchardy C, Breskvar K, Brockmöller J, Cascorbi I, Clapper ML, Coutelle C, Daly A, Dell'Omo M, Dolzan V, Dresler CM, Fryer A, Haugen A, Hein DW, Hildesheim A, Hirvonen A, Hsieh LL, Ingelman-Sundberg M, Kalina I, Kang D, Kihara M, Kiyohara C, Kremers P, Lazarus P, Le Marchand L, Lechner MC, van Lieshout EM, London S, Manni JJ, Maugard CM, Morita S, Nazar-Stewart V, Noda K, Oda Y, Parl FF, Pastorelli R, Persson I, Peters WH, Rannug A, Rebbeck T, Risch A, Roelandt L, Romkes M, Ryberg D, Salagovic J, Schoket B, Seidegard J, Shields PG, Sim E, Sinnet D, Strange RC, Stucker I, Sugimura H, To-Figueras J, Vineis P, Yu MC, Taioli E (2001) Metabolic gene polymorphism frequencies in control populations. Cancer Epidemiol Biomarkers Prev 10:1239–1248
Ghanayem BI, Farooqui MY, Elshabrawy O, Mumtaz MM, Ahmed AE (1991) Assessment of the acute acrylonitrile-induced neurotoxicity in rats. Neurotoxicol Teratol 13:499–502
Ghanayem BI, Sanders M, Chanas B, Burka LT, Gonzalez FJ (1999) Role of cytochrome P-450 2E1 in methacylonitrile metabolism and disposition. J Pharmacol Exp Ther 289:1054–1059
Girre C, Lucas D, Hispard FR, Menez C, Dally S, Menez JP (1994) Assessment of cytochrome P450 2E1 in induction in alcoholic patients by chlorzoxazone pharmacokinetics. Biochem Pharmacol 47:1503–1508
Goasduff T, Cederbaum AI (2000) CYP2E1 degradation by in vitro reconstituted systems: role of the molecular chaperone hsp90. Arch Biochem Biophys 379:321–330
Guengerich FP (1989) Polymorphism of cytochrome P-450 in humans. Trends Pharmacol Sci 10:107–109
Hannon-Fletcher MP, O'Kane MJ, Moles KW, Barnett YA, Barnett CR (2001) Lymphocyte cytochrome P450-CYP2E1 expression in human IDDM subjects. Food Chem Toxicol 39:125–132
Haufroid V, Buchet JP, Gardinal S, Lison D (2002) Cytochrome P4502E1 phenotyping by the measurement of the chlorzoxazone metabolic ratio: assessment of its usefulness in workers exposed to styrene. Int Arch Occup Environ Health 75:453–458
Hayashi S, Watanabe J, Kawajiri K (1991) Genetic polymorphisms in the 5' flanking region change transcriptional regulation of the human cytochrome P450IIE1 gene. J Biochem 110:559–565
Hu Y, Oscarson M, Johansson I, Yue QY, Dahl ML, Tabone M, Arinco S, Albano E, Ingelman-Sundberg M (1997) Genetic polymorphism of human CYP2E1: characterization of two variant alleles. Mol Pharmacol 51:370–376
Hu Y, Hakkola J, Oscarson M, Ingelman-Sundberg M (1999) Structural and functional characterization of the 5'-flanking region of the rat and human cytochrome P450 2E1 genes: identification of a polymorphic repeat in the human gene. Biochem Biophys Res Commun 263:286–293
Hunt CM, Strater S, Stave EM (1990) Effect of normal aging on the activity of human cytochrome P450IIE1. Biochem Pharmacol 40:1666–1669
IARC (1992) 1,3-Butadiene. In: IARC monographs on the evaluation of carcinogenic risks to humans. Volume 54: Occupational exposures to mists and vapours from strong inorganic acids: and other chemicals. International Agency for Research on Cancer, Lyon, pp 237–310
IARC (1994) Acrylamide. In: IARC monographs on the evaluation of carcinogenic risks to humans. Volume 60: Some industrial chemicals. International Agency for Research on Cancer, Lyon, pp 389–433
IARC (1999) Acrylonitrile. In: IARC monographs on the evaluation of carcinogenic risks to Humans. Volume 71, Part 1: Re-evaluation of some organic chemicals, hydrazine and hydrogen peroxide. International Agency for Research on Cancer, Lyon, pp 43–108
Iba MM, Fung J, Gonzalez FJ (2000) Functional Cyp2e1 is required for substantial in vivo formation of 2,5-hexanedione from n-hexane in the mouse. Arch Toxicol 74:582–586
Iwahashi K, Miyatake R, Nakamura K, Suwaki H, Kinoshita H, Ameno K, Ijiri I, Ishikawa Y, Yoneyama H, Mendori T (1995) The ethanol elimination pharmacokinetics—the effects of genotypes of ALDH2 and CYP2E1 on the ethanol metabolism. Arukoru Kenkyuto Yakubutsu Ison 30:63–68
Jackson TE, Lilly PD, Recio L, Schlosser PM, Medinsky MA (2000) Inhibition of cytochrome P450 2E1 decreases, but does not eliminate, genotoxicity mediated by 1,3-butadiene. Toxicol Sci 55:266–273
Jenner P (1998) Oxidative mechanisms in nigral cell death in Parkinson's disease. Mov Disord 13 [Suppl 1]:24–34
Kharasch ED, Thummel KE (1993) Identification of cytochrome P4502E1 as predominant enzyme catalyzing human liver microsomal defluorination of sevoflurane, isoflurane and methoxyflurane. Anesthesiology 79:795–807
Kharasch ED, Thummel KE, Mhzyre J, Lillibridge JH (1993) Single-dose disulfiram inhibition of chlorzoxazone metabolism. Clin Pharmacol Ther 53:643–650
Kim RB, O'Shea D, Wilkinson GR (1995) Interindividual variability of chlorzoxazone 6-hydroxylation in men and women and its relationship to CYP2E1 genetic polymorphisms. Clin Pharmacol Ther 57:645–655
Kim RB, Yamazaki H, Chiba K, O'Shea D, Mimura M, Guengerich FP, Ishizaki T, Shimada T, Wilkinson GR (1996) In vivo and in vitro characterization of CYP2E1 activity in Japanese and Caucasians. J Pharmacol Exp Ther 279:4–11
Kirkovsky LI, Lermontov SA, Zavorin SI, Sukhozhenko II, Zavelsky VI, Thier R, Bolt HM (1998) Hydrolysis of genotoxic methyl-substituted oxiranes: experimental kinetic and semiempirical studies. Environ Toxicol Chem 17:2141–2147
Koop DR, Tierney DJ (1990) Multiple mechanisms in the regulation of ethanol-inducible cytochrome P450IIE1. Bioessays 12:429–435
Laib RJ, Tucholski M, Filser JG, Csanady GA (1992) Pharmacokinetic interaction between 1,3-butadiene and styrene in Sprague-Dawley rats. Arch Toxicol 66:310–314
Le Marchand L, Wilkinson GR, Wilkens LR (1999) Genetic and dietary predictors of CYP2E1 activity: a phenotyping study in Hawaii Japanese using chlorzoxazone. Cancer Epidemiol Biomarkers Prev 8:495–500
Leonard A, Gerber GB, Stecca C, Rueffr J, Borba H, Farmer PB, Sram RJ, Czeizel AE, Kalina I (1999) Mutagenicity, carcinogenicity, and teratogenicity of acrylonitrile. Mutat Res 436:263–283
Lieber CS (1987) Le métabolisme de l' éthanol: hépatotoxicité et interaction avec les médicaments, les carcinogènes et les vitamines. Rev Alcoolisme 32:9–43
Lieber CS (1999) Microsomal ethanol-oxidizing system (MEOS): the first 30 years (1968–1998)—a review. Alcohol Clin Exp Res 23:991–1007
Lieber CS, de Carli LM (1968) Ethanol oxidation by hepatic microsomes: adaptive increase after ethanol feeding. Science 162:917–918
Lipscomp JC, Garrett CM, Snawder JE (1997) Cytochrome P450-dependent metabolism of trichloroethylene: interindividual differences in humans. Toxicol Appl Pharmacol 142:311–318
Lucas D, Menez C, Girre C, Berthou F, Bodenez P, Joannet I, Hispard E, Bardou LG, Menez JF (1995) Cytochrome P450 2E1 genotype and chlorzoxazone metabolism in healthy and alcoholic Caucasian subjects. Pharmacogenetics 5:298–304
Matanoski GM, Santoz-Burgoa C, Zeger SL, Schwartz L (1989) Epidemiologic data related to health effects of 1,3-butadiene. In: Bates DV, Dungworth DL, Lee PN, McClellan RO, Roe FJC (eds) Assessment of inhalation hazards, ILSI monographs, Springer Berlin, pp 202–214
Mayan O, Teixeira JP, Pires AF (2001) Biological monitoring of n-hexane exposure in Portuguese shoe manufacturing workers. Appl Occup Environ Hyg 16:736–741
Mayan O, Teixeira JP, Alves S, Azevedo C (2002) Urinary 2,5 hexanedione as a biomarker of n-hexane exposure. Biomarkers 7:299–305
McCarver DG, Byun R, Hines RN, Hichme M, Wegenek W (1998) A genetic polymorphism in the regulatory sequences of human CYP2E1: association with increased chlorzoxazone hydroxylation in the presence of obesity and ethanol intake. Toxicol Appl Pharmacol 152:276–281
Meskar A, Plee-Gautier Y, Amet Y, Berthou F, Lucas D (2001) Interactions alcool-xénobiotiques. Role du cytochrome P450 2E1. Pathol Biol 49:696–702
Mostafa AM, Abdel-Naim AB, Abo-Salem O, Abdel-Haziz AH, Hamada FM (1999) Renal metabolism of acrylonitrile to cyanide: in vitro studies. Pharmacol Res 40:195–200
Murray JF (2000) TSCA 8(e) submission on health effects in Chinese workers, occupationally exposed to acrylonitrile. Letter and attachments on behalf of the USA AN-group, representing producers and users of acrylonitrile
Nebert DW, Adesnik M, Coon MJ, Estabrook RW, Gonzalez FJ, Guengerich FP, Gunsalus IC, Johnson EF, Kemper B, Levin W, et al. (1987) The P-450 gene superfamily: recommended nomenclature. DNA 6:1–11
Nelson DR, Koymans L, Kamataki T, et al. (1996) P-450 superfamily: update on new sequences, gene mapping, accession numbers, and nomenclature. Pharmacogenetics 6:1–42
Novak RF, Woodcroft KJ (2000) The alcohol-inducible form of cytochrome P450 (CYP 2E1): role in toxicology and regulation of expression. Arch Pharm Res 23:267–282
O'Shea D, Davis SN, Kim RB, Wilkinson GR (1994) Effect of fasting and obesity in humans on the 6-hydroxylation of chlorzoxazone: a putative probe of CYP2E1 activity. Clin Pharmacol Ther 56:359–367
Peng HM, Coon MJ (2000) Promoter function and the role of cytokines in the transcriptional regulation of rabbit CYP2E1 and CYP2E2. Arch Biochem Biophys 382:129–137
Persson I, Johansson I, Bergling H, Dahl ML, Seidegard J, Rylander R, Rannug A, Högberg J, Ingelman-Sundberg M (1993) Genetic polymorphisms of cytochrome P450 2E1 in a Swedish population—relationship to incidence of lung cancer. FEBS Lett 319:207–211
Peter H, Bolt HM (1984) Experimental pharmacokinetics and toxicology of acrylonitrile. G Ital Med Lav 6:77–81
Plee-Gautier E, Foresto F, Ferrara R, Bodénez P, Simon B, Manno M, Berthou F, Lucas D (2001) Genetic repeat polymorphism in the regulating region of CYP2E1: frequency and relationship with enzymatic activity in alcoholics. Alcohol Clin Exp Res 25:800–804
Powell H, Kitteringham NR, Pirmohamed M, Smith DA, Park BK (1998) Expression of cytochrome P4502E1 in human liver: assessment by mRNA, genotype, and phenotype. Pharmacogenetics 8:411–421
Raucy JL, Kraner JC, Lasker JM (1993). Bioactivation of halogenated hydrocarbons by cytochrome P-450E1. Crit Rev Toxicol 23:1–20
Raucy J, Schultz E, Kearins M, Sanjeev A, Johnston D, Ohmdahl J, Eckman L, Carpenter S (1999) CYP2E1 expression in human lymphocytes from various ethnic populations. Alcohol Clin Exp Res 23:1868–1874
Shimada T, Yamazaki H, Mimura M, Inui Y, Guengerich FP (1994) Interindividual variations in human liver cytochrome P-450 enzymes involved in the oxidation of drugs, carcinogens and toxic chemicals: studies with liver microsomes of 30 Japanese and 30 Caucasians. J Pharmacol Exp Ther 270:414–423
Song BF, Gelboin HV, Park SS, Yang CS, Gonzales FJ (1986) Complementary DNA and protein sequences of ethanol-inducible rat and human cytochrome P-450. J Biol Chem 261:16689–16697
Steffens W, Sibbing D, Kiesselbach N, Lewalter J (1998) Behandlung von Patienten mit Vergiftungen durch aliphatische oder olephinische Nitrile. Arbeitsmed Sozialmed Umweltmed 33:479–484
Steffens W, Kehrig B, Lewalter J (2001) Acrylnitril-Intoxikationen—Cyanidbildung und Therapie. Arbeitsmed Sozialmed Umweltmed 36:351–355
Subramanian U, Ahmed AE (1995) Intestinal toxicity of acrylonitrile: in vitro metabolism by intestinal cytochrome P450 2E1. Toxicol Appl Pharmacol 135:1–8
Sumner SC, Fennell TR, Moore TA, Chanas B, Gonzalez F, Ghanayem BI (1999) Role of cytochrome P450 2E1 in the metabolism of acrylamide and acrylonitrile in mice. Chem Res Toxicol 12:1110–1116
Tassaneeyakul W, Veronese ME, Birrett DJ, Gonzalez FJ, Miners JO (1993) Validation of 4-nitrophenol as an in vitro substrate for human liver CYP2E1 using cDNA expression and microsomal kinetic techniques. Biochem Pharmacol 46:1975–1981
Thier R, Bolt HM (2001) The new era of toxicology. Trends Pharmacol Sci 22:549–550
Thier R, Pemble SE, Kramer H, Taylor JB, Guengerich FP, Ketterer B (1996) Human glutathione S-transferase T1-1 enhances mutagenicity of 1,2-dibromoethane, dibromomethane and 1,2,3,4-diepoxybutane in Salmonella typhimurium. Carcinogenesis 17:163–166
Thier R, Lewalter J, Kempkes M, Selinski S, Brüning T, Bolt HM (1999) Haemoglobin adducts of acrylonitrile and ethylene oxide in acrylonitrile workers, dependent on polymorphisms of the glutathione transferases GSTT1 and GSTM1. Arch Toxicol 73:197–202
Thier R, Lewalter J, Bolt HM (2000) Species differences in acrylonitrile metabolism and toxicity between experimental animals and humans based on observations in human accidental poisonings. Arch Toxicol 74:184–189
Thier R, Balkenhol H, Lewalter J, Selinski S, Dommermuth A, Bolt HM (2001) Influence of polymorphisms of the human glutathione transferases and cytochrome P450 2E1 enzyme on the metabolism and toxicity of ethylene oxide and acrylonitrile. Mutat Res 482:41–46
Thier R, Lewalter J, Selinski S, Bolt HM (2002a) Possible impact of human CYP2E1 polymorphisms on the metabolism of acrylonitrile. Toxicol Lett 128:249–255
Thier R, Golka K, Brüning T, Ko Y, Bolt HM (2002b) Genetic susceptibility to environmental toxicants: the interface between human and experimental studies in the development of new toxicological concepts. Toxicol Lett 127:321–327
Thier R, Brüning T, Roos P H, Rihs HP, Golka K, Ko Y, Bolt HM (2002c) Markers of genetic susceptibility in human and environmental hygiene and toxicology. Int J Hyg Environ Health (in press)
Uematsu F, Kikuchi H, Motomiya M, Abe T, Sagami I, Ohmachi T, Wakui A (1991) Association between restriction fragment length polymorphism of the human cytochrome P450 2E1 gene and susceptibility to lung cancer. Jpn J Cancer Res 82:254–256
Umeno M, McBride OW, Yang CS, Gelboin HV, Gonzalez FJ (1988) Human ethanol-inducible P450 2E1: Complete gene sequence, promoter characterization, chromosome mapping and cDNA-direct expression. Biochemistry 27:6731–6735
Vieira I, Sonnier M, Cresteil T (1996) Developmental expression of CYP2E1 in the human liver. Hypermethylation control of gene expression during the neonatal period. Eur J Biochem 238:476–483
Vieira I, Pasanen M, Raunio H, Cresteil T (1998) Expression of CYP2E1 in human lung and kidney during development and in full-term placenta: a differential methylation of the gene is involved in the regulation process. Pharmacol Toxicol 83:183–187
Vogel RA, Kirkendall WM (1984) Acrylonitrile (vinyl cyanide) poisoning: a case report. Tex Med 80:48–51
Wan YY, Cai Y, Li J, Yuan Q, French B, Gonzalez FJ, French S (2001) Regulation of peroxisome proliferator activated receptor alpha-mediated pathways in alcohol fed cytochrome P450 2E1 deficient mice. Hepatol Res 19:117–130
Watanabe J, Hayashi SI, Kawajiri K (1994) Different regulation and expression of the human CYP2E1 gene due to the RsaI polymorphism in the 5'-flanking region. Biochem J 116:321–326
Wei X (1999a) Effects of acrylonitrile on activity of blood cholinesterase. In: Murray JF (ed) TSCA 8(e) submission on health effects in Chinese workers, occupationally exposed to acrylonitrile. Letter and attachments on behalf of the USA AN-group, representing producers and users of acrylonitrile
Wei X (1999b) Tests of four biochemical indices of AN workers. In: Murray JF (ed) TSCA 8(e) submission on health effects in Chinese workers, occupationally exposed to acrylonitrile. Letter and attachments on behalf of the USA AN-group, representing producers and users of acrylonitrile
Woodcroft KJ, Hafner MS, Novak RF (2002) Insulin signaling in the transcriptional and posttranscriptional regulation of CYP2E1 expression. Hepatology 35:263–273
Yoo YSH, Guengerich FP, Yang CS (1988) Metabolism of N-nitrosodialkylamines by human liver microsomes. Cancer Res 48:1499–1504
Zand R, Nelson SD, Slattery JT, Thummel, KE, Kalhorn TF, Adams SP, Wright JM (1993) Inhibition and induction of cytochrome P4502E1-catalyzed oxidation by isoniazid in humans. Clin Pharmacol Ther 54:142–149
Acknowledgement.
The authors thank the European Science Foundation (ESF) for sponsoring the international Genetic Susceptibility to Environmental Toxicants (GENSUT) network during 1998 to 2001.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Bolt, H.M., Roos, P.H. & Thier, R. The cytochrome P-450 isoenzyme CYP2E1 in the biological processing of industrial chemicals: consequences for occupational and environmental medicine. Int Arch Occup Environ Health 76, 174–185 (2003). https://doi.org/10.1007/s00420-002-0407-4
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00420-002-0407-4