Skip to main content

Advertisement

SpringerLink
Log in

Polycyclic aromatic hydrocarbon (PAH) metabolizing enzyme activities in human lung, and their inducibility by exposure to naphthalene, phenanthrene, pyrene, chrysene, and benzo(a)pyrene as shown in the rat lung and liver

  • Metabolic Activation/Inactivation
  • Published:
Archives of Toxicology Aims and scope Submit manuscript

Abstract

In order to survey changes and activities in the polycyclic aromatic hydrocarbon (PAH)-metabolizing enzymes implicated in lung cancer susceptibility studies, we investigated enzyme induction by 2–5-ring-sized ‘biomarker’ PAHs in rat liver and lung, and the activities in five human lung specimens. Naphthalene, phenanthrene, pyrene, chrysene, and benzo[a]pyrene (BaP) were administered to rats for 3 days (25–128 mg/kg/day) and the responses compared with those of model inducers. PAH treatment increased the CYP1A-catalyzed activity of pyrene 1-hydroxylation and 7-ethoxyresorufin O-deethylation in rat liver by up to 28- and 279-fold, and in rat lung by up to 22- and 51-fold, respectively. 1-Naphthol (hUGT1A6), 1-hydroxypyrene (hUGT1A6/1A9), and entacapone (hUGT1A9) are markers of PAH-glucuronidating human uridine diphosphate-glucuronosyltransferases (UGT). These activities increased up to 6.4-fold in rat liver and up to 1.9-fold in rat lung. NADPH:quinone oxidoreductase 1 (NQO1) and glutathione S-transferase activities increased up to 5.3- and 1.6-fold (liver), and up to 4.4- and 1.4-fold (lung), respectively. CYP1A showed the best liver-to-lung relationship (R 2 = 0.90). The inducing efficiency by PAHs differed extensively: control ≤ naphthalene < phenanthrene, pyrene << chrysene < BaP. In human lung (non-smokers), the marker activities of CYP1A1, UGT1A6/1A9, and NQO1 were lower than those in rat lung. Epoxide hydrolase activity was 1,000-fold higher than the pulmonary CYP1A1 activities. Human UGT and NQO1 displayed large variations (>60-fold), many times greater than the experimental (inducible/constitutive) variation in the rat. Kinetics of 1-hydroxypyrene glucuronidation showed two low-K m forms both in rat and human lung. Since the 2–4-ring PAHs (major constituents) were poor enzyme inducers, it appears that the PAH-metabolizing pathways are mainly induced by BaP-type minor constituents. Gene–environmental interactions which magnify polymorphic variability in pulmonary bioactivation/detoxification capacity probably play a key role in individual susceptibility to (or protection against) chemically induced lung cancer. Hence, human exposure to PAH mixtures with high content of BaP-type hydrocarbons confers a potentially higher health risk than PAH mixtures with low content of procarcinogens.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

Abbreviations

ALT:

Alanine aminotransaminase

ANF:

α-Naphthoflavone

BNF:

β-Naphthoflavone

BaP:

Benzo[a]pyrene

BSO:

l-Buthionine-[S,R]-sulfoximine

CDNB:

1-Chloro-2,4-dinitrobenzene

CYP or P450:

Cytochrome P450

DCPIP:

2,6-Dichlorophenolindophenol

EQ:

Ethoxyquin

EROD:

7-Ethoxyresorufin O-deethylase

E-UGT:

Entacapone UGT

GST:

Glutathione S-transferase

HPLC:

High-performance liquid chromatography

MC:

3-Methylcholanthrene

mEH:

Microsomal epoxide hydrolase

NQO1:

NADPH:quinone oxidoreductase 1 [NMO1, quinone reductase, DT-diaphorase]

NP-oxide (EPNP):

1,2-Epoxy-3-(p-nitrophenoxy)propane

NP-diol:

3-[p-Nitrophenoxy]-1,2-propane diol

N-UGT:

1-Naphthol UGT

1-OHP:

1-Hydroxypyrene

PH:

Pyrene 1-hydroxylase

PAH:

Polycyclic aromatic hydrocarbon

UDP:

Uridine diphosphate

UDPGA:

UDP-glucuronic acid

UGT:

UDP-glucuronosyltransferase

References

  • ACGIH (2005) Polycyclic aromatic hydrocarbons (PAHs): BEI®, 7th edn. Documentation ACGIH®. Publication #7DOC-735. American Conference of Governmental Industrial Hygienists, Cincinnati, 17 pp

  • Angerer J, Mannschreck C, Gundel J (1997) Biological monitoring and biochemical effect monitoring of exposure to polycyclic aromatic hydrocarbons (a review). Int Arch Occup Environ Health 70:365–377

    Article  PubMed  CAS  Google Scholar 

  • Anttila S, Lei X-D, Elovaara E, Karjalainen A, Sun W, Vainio H, Hankinson O (2000) An uncommon phenotype of poor inducibility of CYP1A1 in human lung is not ascribable to polymorphisms in the AHR, ARNT, or CYP1A1 genes. Pharmacogenetics 10:741–751

    Article  PubMed  CAS  Google Scholar 

  • Anttila S, Tuominen P, Hirvonen A, Nurminen M, Karjalainen A, Hankinson O, Elovaara E (2001) CYP1A1 levels in lung tissue of tobacco smokers and polymorphisms of CYP1A1 and aromatic hydrocarbon receptor. Pharmacogenetics 11:501–509

    Article  PubMed  CAS  Google Scholar 

  • Asher G, Lotem J, Sachs L, Shaul Y (2004) p53-dependent apoptosis and NAD(P)H:quinone oxidoreductase 1. Meth Enzymol 382(part B):278–293

    Article  PubMed  CAS  Google Scholar 

  • Bock KW, Gschaidmeier H, Heel H, Lehmkoster T, Munzel PA, Raschko F, Bock-Hennig B (1998) AH receptor-controlled transcriptional regulation and function of rat and human UDP-glucuronosyltransferase isoforms. Adv Enzyme Regul 38:207–222

    Article  PubMed  CAS  Google Scholar 

  • Bouchard M, Viau C (1999) Urinary 1-hydroxypyrene as a biomarker of exposure to polycyclic aromatic hydrocarbons: biological monitoring strategies and methodology for determining biological exposure indices for various work environments. Biomarkers 4:159–187, and references therein

    Google Scholar 

  • Buetler TM, Gallagher EP, Wang C, Stahl DL, Hayes JD, Eaton DL (1995) Induction of phase I and phase II drug-metabolizing enzyme mRNA, protein, and activity by BHA, ethoxyquin, and oltipraz. Toxicol Appl Pharmacol 135:45–57

    Article  PubMed  CAS  Google Scholar 

  • Burchell B, Brierley CH, Monaghan CH, Clarke DJ (1998) The structure and function of the UDP-glucuronosyltransferase gene family. Adv Pharmacol 42:335–338

    Article  PubMed  CAS  Google Scholar 

  • Conney AH (1982) Induction of microsomal enzymes by foreign chemicals and carcinogen by polycyclic aromatic hydrocarbons: GHA Clowes Memorial Lecture. Cancer Res 42:4875–4917

    PubMed  CAS  Google Scholar 

  • Elovaara E, Engström K, Nakajima T, Park SS, Gelboin HV, Vainio H (1991) Metabolism of inhaled styrene in acetone-, phenobarbital-, and 3-methylcholanthrene pretreated rats: stimulation and stereochemical effects by induction of cytochromes P450IIE1, P450IIB and P450IA. Xenobiotica 21:651–661

    Article  PubMed  CAS  Google Scholar 

  • Elovaara E, Heikkilä P, Pyy L, Mutanen P, Riihimäki V (1995a) Significance of dermal and respiratory uptake in creosote workers: exposure to polycyclic aromatic hydrocarbons and urinary excretion of 1-hydroxypyrene. Occup Environ Med 52:196–203

    Article  CAS  Google Scholar 

  • Elovaara E, Raunio H, Pelkonen O, Vainio H (1995b) Oxidation of pyrene in human liver and lungs. Hum Exp Toxicol 14:821

    Google Scholar 

  • Elovaara E, Karjalainen A, Vanhala E, Anttila S, Luukkanen L, Vainio H (1997) Effect of asbestos on PAH-metabolizing enzyme activities in lungs from smoking and non-smoking lung cancer surgery patients. In: ISSX proceedings (6th European ISSX Meeting), Göteborg, Sweden, vol. 11, p 64

  • Elovaara E, Mikkola J, Luukkanen L, Antonio L, Fournel-Gigleux S, Burchell B, Magdalou J, Taskinen J (2004) Assessment of catechol induction and glucuronidation in rat liver microsomes. Drug Metab Dispos 32:1426–1433

    Article  PubMed  CAS  Google Scholar 

  • Ernster L (1967) DT diaphorase. Meth Enzymol 10:309–317

    Article  CAS  Google Scholar 

  • Gelboin HV (1980) Benzo(alpha)pyrene metabolism, activation and carcinogenesis: role and regulation of mixed-function oxidases and related enzymes. Physiol Rev 60:1107–1166

    PubMed  CAS  Google Scholar 

  • Giuliano KA, Lau EP, Fall RR (1980) Simplified liquid chromatographic assay for epoxide hydrolase. J Chromatogr 202:447–452

    Article  PubMed  CAS  Google Scholar 

  • Grainger J, Huang W, Li Z, Selvin E, Walcott C, Smith C, Turner WE, Wang R, Patterson DG Jr (2004) PAH reference range levels in the U.S. population by measurement of urinary monohydroxy metabolites. Polycyclic Aromatic Comp 24:385–404

    Article  CAS  Google Scholar 

  • Grimmer G, Jacob J, Dettbarn G, Naujack KW (1997) Determination of urinary metabolites of polycyclic aromatic hydrocarbons (PAH) for the risk assessment of PAH-exposed workers. Int Arch Occup Environ Health 69:231–239

    Article  PubMed  CAS  Google Scholar 

  • Guengerich FP (2000) Metabolism of chemical carcinogens. Carcinogenesis 21:345–351

    Article  PubMed  CAS  Google Scholar 

  • Gundel J, Schaller KH, Angerer J (2000) Occupational exposure to polycyclic aromatic hydrocarbons in a fireproof stone producing plant: biological monitoring of 1-hydroxypyrene, 1-, 2-, 3- and 4-hydroxyphenanthrene, 3-hydroxybenz(a)anthracene and 3-hydroxybenzo(a)pyrene. Int Arch Occup Environ Health 73:270–274

    Article  PubMed  CAS  Google Scholar 

  • Habig WH, Pabst MJ, Jacoby WB (1974) Glutathione S-transferases. The first step in mercapturic acid formation. J Biol Chem 249:7130–7139

    PubMed  CAS  Google Scholar 

  • Hayes JD, Pulford DJ (1995) The glutathione S-transferase supergene family. Regulation of GST and the contribution of the isozymes to cancer chemoprotection and drug resistance. Crit Rev Biochem Mol Biol 30:455–600

    Google Scholar 

  • Hayes JD, Flanagan JU, Jowsey IR (2005) Glutathione transferases. Annu Rev Pharmacol Toxicol 45:51–88

    Article  PubMed  CAS  Google Scholar 

  • Hecht SS (2002) Human urinary carcinogen metabolites: biomarkers for investigating tobacco and cancer. Carcinogenesis 23:907–922

    Article  PubMed  CAS  Google Scholar 

  • Huang W, Grainger J, Patterson DG Jr, Turner WE, Caudill SP, Needham LL, Pirkle JL, Sampson EJ (2004) Comparison of 1-hydroxypyrene exposure in the US population with that in occupational exposure studies. Int Arch Occup Environ Health 77:491–498

    Article  PubMed  CAS  Google Scholar 

  • Hukkanen J, Pelkonen O, Hakkola J, Raunio H (2002) Expression and regulation of xenobiotic-metabolizing enzymes cytochrome P450 (CYP) enzymes in human lung. Crit Rev Toxicol 32:391–411

    Article  PubMed  CAS  Google Scholar 

  • IARC (1985) IARC monographs on the evaluation of the carcinogenic risk of chemicals to humans, vol. 35, Polynuclear aromatic compounds. Part 4, Bitumens, coal-tars and derived products, shale oils and soots. IARC, Lyon, France

  • Jacob J, Schmoldt A, Grimmer G (1982) Influence of monooxygenase inducers on the metabolic profile of phenanthrene in rat liver microsomes. Toxicology 25:333–343

    Article  PubMed  CAS  Google Scholar 

  • Jaiswal AK (2000) Regulation of genes encoding NAD(P)H:quinone oxidoreductases. Free Radic Biol Med 29:254–262

    Article  PubMed  CAS  Google Scholar 

  • Jinno H, Saeki M, Saito Y, Tanaka-Kagawa T, Hanioka N, Sai K, Kaniwa N, Ando M, Shirao K, Minami H, Ohtsu A, Yoshida T, Saijo N, Ozawa S, Sawada J (2003) Functional characterization of human UDP-glucuronosyltransferase 1A9 variant, D256N, found in Japanese cancer patients. J Pharmacol Exp Ther 306:688–693

    Article  PubMed  CAS  Google Scholar 

  • Joseph P, Jaiswal AK (1994) NAD(P)H:quinone oxidoreductase1 (DT diaphorase) specifically prevents the formation of benzo[a]pyrene quinone-DNA adducts generated by cytochrome P4501A1 and P450 reductase. Proc Natl Acad Sci USA 91:8413–8417

    Article  PubMed  CAS  Google Scholar 

  • Keski-Hynnilä H, Raanaa K, Forsberg M, Männistö P, Taskinen J, Kostiainen R (2001) Quantitation of entacapone glucuronide in rat plasma by on-line coupled restricted access media column and liquid chromatography–tandem mass spectrometry. J Chromatogr B Biomed Sci Appl 759:227–236

    Article  PubMed  Google Scholar 

  • Kim JH, Sherman ME, Curriero FC, Guengerich FP, Strickland PT, Sutter TR (2004a) Expression of cytochromes P450 1A1 and 1B1 in human lung from smokers, non-smokers, and ex-smokers. Toxicol Appl Pharmacol 199:210–219

    Article  CAS  Google Scholar 

  • Kim YD, Todoroki H, Oyama T, Isse T, Matsumoto A, Yamaguchi T, Kim H, Uchiyama I, Kawamoto T (2004b) Identification of cytochrome P450 isoforms involved in 1-hydroxylation of pyrene. Environ Res 94:262–266

    Article  CAS  Google Scholar 

  • Kiyohara C, Otsu A, Shirakawa T, Fukuda S, Hopkin JM (2002) Genetic polymorphisms and lung cancer susceptibility: a review. Lung Cancer 37:241–256

    Article  PubMed  Google Scholar 

  • Koley AP, Buters JTM, Robinson RC, Markowitz A, Friedman FK (1997) Differential mechanisms of cytochrome P450 inhibition and activation by alpha-naphthoflavone. J Biol Chem 272:3149–3152

    Article  PubMed  CAS  Google Scholar 

  • Lowry O, Rosebrough N, Farr L, Randall R (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193:265–275

    PubMed  CAS  Google Scholar 

  • Luukkanen L, Elovaara E, Lautala P, Taskinen J, Vainio H (1997) Characterization of 1-hydroxypyrene as a novel marker substrate of 3-methylcholanthrene-inducible phenol UDP-glucuronosyltransferase(s). Pharmacol Toxicol 80:152–158

    Article  PubMed  CAS  Google Scholar 

  • Luukkanen L, Mikkola J, Forsman T, Taavitsainen P, Taskinen J, Elovaara E (2001) Glucuronidation of 1-hydroxypyrene by human liver microsomes and human UDP-glucuronosyltransferases UGT1A6, UGT1A7, and UGT1A9: development of a high-sensitivity glucuronidation assay for human tissue. Drug Metab Dispos 29:1096–1101

    PubMed  CAS  Google Scholar 

  • Luukkanen L, Taskinen J, Kurkela M, Kostiainen R, Hirvonen J, Finel M (2005) Kinetic characterization of the 1A subfamily of recombinant human UDP-glucuronosyltransferases. Drug Metab Dispos 33:1017–1026

    Article  PubMed  CAS  Google Scholar 

  • Manning BW, Franklin MR (1990) Induction of rat UDP-glucuronosyltransferase and glutathione S-transferase activities by l-buthionine-S,R-sulfoximine without induction of cytochrome P-450. Toxicology 65:149–159

    Article  PubMed  CAS  Google Scholar 

  • Myllynen P, Pasanen M, Pelkonen O (2005) Human placenta: a human organ for developmental toxicology research and biomonitoring. Placenta 26:361–371 (review)

    Google Scholar 

  • Nakajima T, Elovaara E, Anttila S, Hirvonen A, Camus A-M, Hayes JD, Ketterer B, Vainio H (1995) Expression and polymorphism of glutathione S-transferases in human lungs: risk factors in smoking-related lung cancer. Carcinogenesis 16:707–711

    Article  PubMed  CAS  Google Scholar 

  • Nebert DW, Dalton TP, Okey AB, Gonzalez FJ (2004) Role of aryl hydrocarbon receptor-mediated induction of the CYP1 enzymes in environmental toxicity and cancer. J Biol Chem 23:23847–23850

    Article  Google Scholar 

  • Nioi P, Hayes JD (2004) Contribution of NAD(P)H:quinone oxidoreductase 1 to protection against carcinogenesis, and regulation of its gene by Nrf2 basic-region zipper and the arylhydrocarbon receptor basic helix-loop-helix transcription factors. Mutat Res 555:149–171

    PubMed  CAS  Google Scholar 

  • Paakki P, Stockmann H, Kantola M, Wagner P, Lauper U, Huch R, Elovaara E, Kirkinen P, Pasanen M (2000) Maternal drug abuse and human placental term xenobiotic and steroid metabolizing enzymes in vitro. Environ Health Perspect 108:141–145

    Article  PubMed  CAS  Google Scholar 

  • Pelkonen O, Nebert D (1982) Metabolism of polycyclic aromatic hydrocarbons: etiologic role in carcinogenesis. Pharmacol Rev 34:189–221

    PubMed  CAS  Google Scholar 

  • Pelkonen O, Pasanen M, Kuha H, Gachalyi B, Kairaluoma M, Sotaniemi EA, Park SS, Friedman FK, Gelboin HV (1986) The effect of cigarette smoking on 7-ethoxycoumarin O-deethylase and other monooxygenase activities in human liver: analyses with monoclonal antibodies. Br J Clin Pharmacol 22:125–134

    PubMed  CAS  Google Scholar 

  • Pelkonen O, Raunio H, Rautio A, Lang M (1999) Xenobiotic-metabolizing enzymes and cancer risk: correspondence between genotype and phenotype. IARC Sci Publ 148:77–88 (review)

    Google Scholar 

  • Penning TM, Burczynski ME, Hung CF, McCoull KD, Palackal NT, Tsuruda LS (1999) Dihydrodiol dehydrogenases and polycyclic aromatic hydrocarbon activation: generation of reactive and redox active o-quinones. Chem Res Toxicol 12:1–18 (review)

    Google Scholar 

  • Prough RA, Burke MD, Mayer RT (1978) Direct fluorometric methods for measuring mixed-function oxidase activity. Meth Enzymol 52(part C):373–377

    Google Scholar 

  • Ross D, Siegel D (2004) NAD(P)H:quinone oxidoreductase 1 (NQO1, DT-diaphorase) functions and pharmacogenetics. Meth Enzymol 382(part B):115–144

    Article  PubMed  CAS  Google Scholar 

  • Schlager JJ, Powis G (1990) Cytosolic NAD(P)H:(quinone-acceptor)oxidoreductase in human normal and tumor tissue: effects of cigarette smoking and alcohol. Int J Cancer 45:403–409

    Article  PubMed  CAS  Google Scholar 

  • Shimada T, Fujii-Kuriyama Y (2004) Metabolic activation of polycyclic aromatic hydrocarbons to carcinogens by cytochrome P450 1A1 and 1B1. Cancer Sci 95:1–6

    Article  PubMed  CAS  Google Scholar 

  • Shimada T, Yun CH, Yamazaki H, Gautier JC, Beaune PH, Guengerich FP (1992) Characterization of human lung microsomal cytochrome P-450 1A1 and its role in the oxidation of chemical carcinogens. Mol Pharmacol 41:856–864

    PubMed  CAS  Google Scholar 

  • Shou M, Grogan J, Mancewicz JA, Krausz KW, Gonzalez FJ, Gelboin HV, Korzekwa KR (1994) Activation of CYP3A4: evidence for the simultaneous binding of two substrates in a cytochrome P450 active site. Biochemistry 33:6450–6455

    Article  PubMed  CAS  Google Scholar 

  • Thier R, Bruning T, Roos PH, Rihs H-P, Golka K, Ko Y, Bolt HM (2003) Markers of genetic susceptibility in human environmental hygiene and toxicology: the role of selected CYP, NAT and GST genes. Int J Hyg Environ Health 206:149–171

    Article  PubMed  CAS  Google Scholar 

  • UBA (1998) Umweltbundesamt: Umwelt-Survey, Berlin 1998. http://www.umweltbundesamt.de/survey/us98/pak.htm

  • Vainio H, Elovaara E, Luukkanen L, Anttila S, Ulmanen I, Fournel-Gigleux S, Ouzzine M, Pillot T, Magdalou M (1995) Expression and co-induction of CYP1A1 and UGT1*6 in human lungs. Eur J Drug Metab Pharmacokinet 20:47–48

    CAS  Google Scholar 

  • Vineis P (2004) Individual susceptibility to carcinogens. Oncogene 23:6477–6483

    Article  PubMed  CAS  Google Scholar 

  • Wells PG, Mackenzie PI, Chowdhury JR, Guillemette C, Gregory PA, Ishii Y, Hansen AJ, Kessler FK, Kim PM, Chowdhury NR, Ritter JK (2004) Glucuronidation and the UDP-glucuronosyltransferases in health and disease. Drug Metab Dispos 32:281–290 (review)

    Google Scholar 

  • Yang M, Koga M, Katoh T, Kawamoto T (1999) A study for the proper application of urinary naphthols, new biomarkers for airborne polycyclic aromatic hydrocarbons. Arch Environ Contam Toxicol 36:99–108

    Article  PubMed  CAS  Google Scholar 

  • Ye Z, Song H, Higgins JP, Pharoah P, Danesh J (2006) Five glutathione S-transferase gene variants in 23,452 cases of lung cancer and 30,397 controls: meta-analysis of 130 studies. PLoS Med 3(4):e91 [Epub 2006 March 7]

    Google Scholar 

  • Zheng Z, Fang JL, Lazarus P (2002) Glucuronidation: an important mechanism for detoxification of benzo[a]pyrene in aerodigestive tract tissues. Drug Metab Dispos 30:397–403

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

We wish to thank Ms. Maria Pihlaja and Ms. Ulla Peltonen for skillful technical assistance. UGT studies were associated with the BMH4-CT97-2621 project supported by the Commission of the European Communities.

Author information

Author notes

  1. Leena Luukkanen

    Present address: Division of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Helsinki, 00014, Helsinki, Finland

  2. Markku Pasanen

    Present address: Department of Pharmacology and Toxicology, University of Kuopio, Kuopio, Finland

Authors and Affiliations

  1. Finnish Institute of Occupational Health, 00250, Helsinki, Finland

    Eivor Elovaara, Jouni Mikkola, Helene Stockmann-Juvala, Leena Luukkanen & Harri Vainio

  2. Division of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Helsinki, 00014, Helsinki, Finland

    Helena Keski-Hynnilä & Risto Kostiainen

  3. Department of Pharmacology and Toxicology, University of Oulu, Oulu, Finland

    Markku Pasanen & Olavi Pelkonen

Authors
  1. Eivor Elovaara
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jouni Mikkola
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Helene Stockmann-Juvala
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Leena Luukkanen
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Helena Keski-Hynnilä
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Risto Kostiainen
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Markku Pasanen
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Olavi Pelkonen
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Harri Vainio
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Eivor Elovaara.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Elovaara, E., Mikkola, J., Stockmann-Juvala, H. et al. Polycyclic aromatic hydrocarbon (PAH) metabolizing enzyme activities in human lung, and their inducibility by exposure to naphthalene, phenanthrene, pyrene, chrysene, and benzo(a)pyrene as shown in the rat lung and liver. Arch Toxicol 81, 169–182 (2007). https://doi.org/10.1007/s00204-006-0135-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00204-006-0135-8

Keywords

Search

Navigation