Cytochrome P450-mediated pulmonary metabolism of carcinogens: Regulation and cross-talk in lung carcinogenesis

American Journal of Respiratory Cell and Molecular Biology

Volumn 44, Issue 5, 2011, Pages 583-590

  Anttila, Sisko ^a   Raunio, Hannu ^b   Hakkola, Jukka ^c  

^a HELSINKI UNIVERSITY CENTRAL HOSPITAL   (Finland)

^b UNIVERSITY OF EASTERN FINLAND   (Finland)

^c UNIVERSITY OF OULU   (Finland)

Author keywords

AHR; CYP; NRF2; Oxidative stress; Tobacco carcinogens

Indexed keywords

AROMATIC HYDROCARBON RECEPTOR; ASBESTOS; CYTOCHROME P450; ESTROGEN RECEPTOR; KELCH LIKE ECH ASSOCIATED PROTEIN 1; NITROSAMINE; REACTIVE OXYGEN METABOLITE; TOBACCO SMOKE; TRANSCRIPTION FACTOR NF E2;

CANCER RISK; ENVIRONMENTAL FACTOR; ENZYME LOCALIZATION; ENZYME METABOLISM; GENETIC SUSCEPTIBILITY; HUMAN; LUNG CANCER; LUNG CARCINOGENESIS; MOLECULAR INTERACTION; NONHUMAN; OXIDATIVE STRESS; PROTEIN EXPRESSION; REVIEW; TRANSCRIPTION REGULATION; XENOBIOTIC METABOLISM;

BIOTRANSFORMATION; CARCINOGENS; CYTOCHROME P-450 ENZYME SYSTEM; GENE EXPRESSION REGULATION, NEOPLASTIC; HUMANS; LUNG; LUNG NEOPLASMS; NF-E2-RELATED FACTOR 2; OXIDATIVE STRESS; POLYCYCLIC HYDROCARBONS, AROMATIC; RECEPTORS, ARYL HYDROCARBON; RISK FACTORS; SMOKING; TOBACCO; TRANSCRIPTION FACTORS;

NICOTIANA TABACUM;

EID: 79955512616     PISSN: 10441549     EISSN: None     Source Type: Journal    
DOI: 10.1165/rcmb.2010-0189RT     Document Type: Review

References (88)

1. International Agency for Research on Cancer. IARC monographs on the Evaluation of Carcinogenic Risks to Humans, vol. 83. Tobacco smoke and involuntary smoking. Lyon, FRance: IARC; 2004. pp. 53-119.
2. Heintz NH, Janssen-Heiniger YM, Mossman BT. Asbestos, lung cancers, and mesotheliomas: from molecular approaches to targeting tumor survival pathways. Am J Respir Cell Mol Biol 2010;42:133-139.
3. Dennissenko MF, Pao A, Tang M, Pfeifer GP. Preferential formation of benzo[a]pyrene adducts at lung cancer mutational hot spots in P53. Science 1996;274:430-432. (Pubitemid 26353359)
4. Phillips DH. Smoking-related DNA and protein adducts in human tissues. Carcinogenesis 2002;23:1979-2004.
5. Mollerup S, Berge G, Bære R, Skaug V, Hewer A, Phillips DH, Stangeland L, Haugen A. Sex differences in risk of lung cancer: expression of genes in the PAH bioactivation pathway in relation to smoking and bulky DNA adducts. Int J Cancer 2006;119:741-744. (Pubitemid 44051435)
6. Anttila S, Hukkanen J, Hakkola J, Stjernvall T, Beaune P, Edwards RJ, Boobis AR, Pelkonen O, Raunio H. Expression and localization of CYP3A4 and CYP3A5 in human lung. Am J Respir Cell Mol Biol 1997;16:242-249. (Pubitemid 127497446)
7. Wynder EL, Muscat JE. The changing epidemiology of smoking and lung cancer histology. Environ Health Perspect 1995;103:143-148. (Pubitemid 26040890)
8. Hecht SS. Cigarette smoking: cancer risks, carcinogens, and mechanisms. Langenbecks Arch Surg 2006;391:603-613. (Pubitemid 44657742)
9. Hecht SS. Progress and challenges in selected areas of tobacco carcinogenesis. Chem Res Toxicol 2008;21:160-171. (Pubitemid 351219717)
10. Shimada T, Yamasaki H, Mimura M, Wakamiya N, Ueng Y-F, Guengerich FP, Inui Y. Characterization of microsomal cytochrome P450 enzymes involved in the oxidation of xenobiotic chemicals in human fetal livers and adult lungs. Drug Metab Dispos 1996;24:515-522. (Pubitemid 26143771)
11. Shimada T. Xenobiotic-metabolizing enzymes involved in activation and detoxification of carcinogenic polycyclic aromatic hydrocarbons. Drug Metab Pharmacokinet 2006;21:257-276.
12. Anttila S, Hietanen E, Vainio H, Camus A-M, Gelboin HV, Park SS, Heikkilä L, Karjalainen A, Bartsch H. Smoking and peripheral type of cancer are related to high levels of pulmonary cytochrome P450IA in lung cancer patients. Int J Cancer 1991;47:681-685.
13. Willey JC, Coy E, Brolly C, Utell MJ, Frampton MW, Hammerslay J, Thilly WG, Olson D, Cairns K. Xenobiotic metabolism enzyme gene expression in human bronchial epithelial and alveolar macrophage cells. Am J Respir Cell Mol Biol 1996;14:262-271. (Pubitemid 126439820)
14. Saarikoski ST, Husgafvel-Pursiainen K, Hirvonen A, Vainio H, Gonzalez FJ, Anttila S. Localization of CYP1A1 mRNA in human lung by in situ hybridization: comparison with immunohistochemical findings. Int J Cancer 1998;77:33-39. (Pubitemid 28308549)
15. Fujii-Kuriyama Y, Kawajiri K. Molecular mechanisms of the physiological functions of the aryl hydrocarbon (dioxin) receptor, a multifunctional regulator that senses and responds to environmental stimuli. Proc Jpn Acad, Ser B, Phys Biol Sci 2010;86:40-53.
16. Bui PH, Hankinson O. Functional characterization of human cytochrome P450 2S1 using a synthetic gene-expressed protein in Escherichia coli. Mol Pharmacol 2009;76:1031-1043.
17. Uppstad H, Øvrebø S, Haugen A, Mollerup S. Importance of CYP1A1 and CYP1B1 in bioactivation of benzo[a]pyrene in human lung cell lines. Toxicol Lett 2010;192:221-228.
18. Hukkanen J, Hakkola J, Anttila S, Piipari R, Karjalainen A, Pelkonen O, Raunio H. Detection of mRNA encoding xenobiotic-metabolizing cytochrome P450s in human bronchoalveolar macrophages and peripheral blood lymphocytes. Mol Carcinog 1997;20:224-230. (Pubitemid 27508886)
19. Macé K, Bowman ED, Vautravers P, Shields PG, Harris CC, Pfeifer AM. Characterisation of xenobiotic-metabolising enzyme expression in human bronchial mucosa and peripheral lung tissues. Eur J Cancer 1998;34:914-920. (Pubitemid 28248506)
20. Rylander T, Neve EPA, Ingelman-Sundberg M, Oscarson M. Identification and tissue distribution of the novel human cytochrome P450 2S1 (CYP2S1). Biochem Biophys Res Commun 2001;281:529-535. (Pubitemid 32928187)
21. Rivera SP, Saarikoski ST, Hankinson O. Identification of a novel dioxin-inducible cytochrome P450. Mol Pharmacol 2002;61:255-259. (Pubitemid 34112798)
22. Wei C, Caccavale RJ, Weyand EH, Chen S, Iba MM. Induction of CYP1A1 and CYP1A2 expressions by prototypic and atypical inducers in the human lung. Cancer Lett 2002;178:25-36. (Pubitemid 34159238)
23. Kim JH, Sherman ME, Curriero FC, Guengerich FP, Strickland PT, Sutter TR. Expression of cytochromes P450 1A1 and 1B1 in human lung from smokers, non-smokers, and ex-smokers. Toxicol Appl Pharmacol 2004;199:210-219. (Pubitemid 39208722)
24. Thum T, Erpenbeck VJ, Moeller J, Hochfeld JM, Krug N, Borlak J. Expression of xenobiotic metabolizing enzymes in different lung compartments of smokers and nonsmokers. Environ Health Perspect 2006;114:1655-1661. (Pubitemid 44718269)
25. Nebert DW, Dalton TP, Okey AB, Gonzalez FJ. Role of aryl hydrocarbon receptor-mediated induction of the CYP1 enzymes in environmental toxicity and cancer. J Biol Chem 2004;279:23847-23850. (Pubitemid 38725238)
26. Cheung C, Gonzalez FJ. Humanized mouse lines and their application for prediction of human drug metabolism and toxicological risk assessment. J Pharmacol Exp Ther 2008;327:288-299.
27. Xie H-G, Wood AJJ, Kim RB, Stein CM, Wilkinson GR. Genetic variability in CYP3A5 and its possible consequences. Pharmacogenomics 2004;5:243-272. (Pubitemid 38499965)
28. Kuehl P, Zhang J, Lin Y, Lamba J, Assem M, Schuetz J, Watkins PB, Daly A, Wrighton SA, Hall SD, et al. Sequence diversity in CYP3A promoters and characterization of the genetic basis of polymorphic CYP3A5 expression. Nat Genet 2001;27:383-391. (Pubitemid 32268418)
29. Weng Y, Fang C, Turesky RJ, Behr M, Kaminsky LS, Ding X. Determination of the role of target tissue metabolism in lung carcinogenesis using conditional cytochrome P450 reductase-null mice. Cancer Res 2007;67:7825-7832. (Pubitemid 47281377)
30. Crawford EL, Weaver DA, DeMuth JP, Jackson CM, Khuder SA, Frampton MW, Utell MJ, Thilly WG, Willey JC. Measurement of cytochrome P450 2A6 and 2E1 gene expression in primary human bronchial epithelial cells. Carcinogenesis 1998;19:1867-1871. (Pubitemid 28474654)
31. Su T, Bao Z, Zhang Q-Y, Smith TJ, Hong J-Y, Ding X. Human cytochrome P450 CYP2A13: predominant expression in the respiratory tract and its high efficiency metabolic activation of a tobacco-specific carcinogen, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone. Cancer Res 2000;60:5074-5079.
32. Runge DM, Stock TW, Lehmann T, Taege C, Bernauer U, Stolz DB, Hofmann S, Foth H. Expression of cytochrome P450 2E1 in normal human bronchial epithelial cells and activation by ethanol in culture. Arch Toxicol 2001;5:335-345. (Pubitemid 32757415)
33. Zhu L-R, Thomas PE, Lu G, Reuhl KR, Yang G-Y, Wang L-D, Wang S-L, Yang CS, He X-Y, Hong J-Y. CYP2A13 in human respiratory tissues and lung cancers: an immunohistochemical study with a new peptide-specific antibody. Drug Metab Dispos 2006;34:1672-1676. (Pubitemid 44427469)
34. Schlicht KE, Berg JZ, Murphy SE. Effect of CYP2A13 active site mutation N297A on metabolism of coumarin and tobacco-specific nitrosamines. Drug Metab Dispos 2009;37:665-671.
35. Kim H-R, Lee G-H, Cho EY, Chae S-W, Ahn T, Chae H-J. Bax inhibitor 1 regulates ER-stress-induced ROS accumulation through the regulation of cytochrome P450 2E1. J Cell Sci 2009;122:1126-1133.
36. Carr BA, Wan J, Hines RN, Yost GS. Characterization of the human lung CYP2F1 gene and identification of a novel lung-specific binding motif. J Biol Chem 2003;278:15473-15483. (Pubitemid 36799654)
37. Wan J, Carr BA, Cutler NS, Lanza DL, Hines RN, Yost GS. Sp1 and Sp3 regulate basal transcription of the human CYP2F1 gene. Drug Metab Dispos 2005;33:1244-1253. (Pubitemid 41043769)
38. Poch MT, Cutler NS, Yost GS, Hines RN. Molecular mechanisms regulating human CYP4B1 lung-selective expression. Drug Metab Dispos 2005;33:1174-1184. (Pubitemid 41043761)
39. Kivistö KT, Griese E-U, Fritz P, Linder A, Hakkola J, Raunio H, Beaune P, Kroemer HK. Expression of cytochrome P450 3A enzymes in human lung: a combined RT-PCR and immunohistochemical analysis of normal tissue and lung tumours. Naunyn Schmiedebergs Arch Pharmacol 1996;353:207-212.
40. Raunio H, Hakkola J, Pelkonen O. Regulation of CYP3A genes in the human respiratory tract. Chem Biol Interact 2005;151:53-62. (Pubitemid 40208557)
41. Biggs JS,Wan J, Cutler NS, Hakkola J, Uusimäki P, Raunio H, Yost GS. Transcription factor binding to a putative double E-Box motif represses CYP3A4 expression in human lung cells. Mol Pharmacol 2007;72:514-525. (Pubitemid 47347286)
42. Vieira I, Pasanen M, Raunio H, Cresteil T. 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 1998;83:183-187. (Pubitemid 28512134)
43. Ling G, Wei Y, Ding X. Transcriptional regulation of human CYP2A13 expression in the respiratory tract by CCAAT/enhancer binding protein and epigenetic modulation. Mol Pharmacol 2007;71:807-816. (Pubitemid 46294092)
44. Pavek P, Dvorak Z. Xenobiotic-induced transcriptional regulation of xenobiotic metabolizing enzymes of the cytochrome P450 superfamily in human extrahepatic tissues. Curr Drug Metab 2008;9:129-143. (Pubitemid 351461002)
45. Chiaro CR, Patel RD, Marcus CB, Perdew GH. Evidence for an aryl hydrocarbon receptor-mediated cytochrome p450 autoregulatory pathway. Mol Pharmacol 2007;72:1369-1379. (Pubitemid 350012610)
46. Hukkanen J, Lassila A, Päivärinta K, Valanne S, Sarpo S, Hakkola J, Pelkonen O, Raunio H. Induction and regulation of xenobiotic-metabolizing cytochrome P450s in the human A549 lung adenocarcinoma cell line. Am J Respir Cell Mol Biol 2000;22:360-366. (Pubitemid 30343363)
47. Anttila S, Hakkola J, Tuominen P, Elovaara E, Husgafvel-Pursiainen K, Karjalainen A, Hirvonen A, Nurminen T. Methylation of CYP1A1 promoter in lung is associated with tobacco smoking. Cancer Res 2003;63:8623-8628. (Pubitemid 38064036)
48. Weems JM, Yost GS. 3-Methylindole metabolites induce lung CYP1A1 and CYP2F1 enzymes by AhR and non-AhR mechanisms, respectively. Chem Res Toxicol 2010;23:696-704.
49. Hukkanen J, Väisänen T, Lassila A, Piipari R, Anttila S, Pelkonen O, Raunio H, Hakkola J. Regulation of CYP3A5 by glucocorticoids and cigarette smoke in human lung-derived cells. J Pharmacol Exp Ther 2003;304:745-752. (Pubitemid 36152353)
50. Casado FL, Singh KP, Gasiewicz TA. The aryl hydrocarbon receptor: regulation of hematopoiesis and involvement in the progression of blood diseases. Blood Cells Mol Dis 2010;44:199-206.
51. Tian Y. Ah receptor and NF-κB interplay on the stage of epigenome. Biochem Pharmacol 2009;77:670-680.
52. Vogel CFA, Matsumura F. A new cross-talk between the aryl hydrocarbon receptor and RelB, a member of the NF-κB family. Biochem Pharmacol 2009;77:734-745.
53. Baglole CJ, Maggirwar SB, Gasiewicz TA, Thatcher TH, Phipps RP, Sime PJ. The aryl hydrocarbon receptor attenuates tobacco smoke-induced cyclooxygenase-2 and prostaglandin production in lung fibroblasts through regulation of the NF-κB family member RelB. J Biol Chem 2008;283:28944-28957.
54. Haegens A, Barrett TF, Gell J, Shukla A, MacPherson M, Vacek P, Poynter ME, Butnor KJ, Janssen-Heininger YM, Steele C, et al. Airway epithelial NF-(kappa)B activation modulates asbestos-induced inflammation and mucin production in vivo. J Immunol 2007;178:1800-1808. (Pubitemid 46154652)
55. Rish HA, Howe GR, Jain M, Burch JD, Holloway EJ, Miller AB. Are female smokers at higher risk of lung cancer than male smokers? Am J Epidemiol 1993;138:281-293.
56. Henschke CI, Miettinen OS. Women's susceptibility to tobacco carcinogens. Lung Cancer 2004;43:1-5. (Pubitemid 38096286)
57. Bain C, Feskanich D, Speizer FE, Thun M, Hertzmark E, Rosner BA, Colditz GA. Lung cancer rates in men and women with comparable histories of smoking. J Natl Cancer Inst 2004;96:826-834. (Pubitemid 38807603)
58. Freedman ND, Leitzmann MF, Hollenbeck AR, Schatzkin A, Abnet CC. Cigarette smoking and subsequent risk of lung cancer in men and women: analysis of a prospective cohort study. Lancet Oncol 2008;9:649-656.
59. Kure EH, Ryberg D, Hewer A, Phillips DH, Skaug V, Baera R, Haugen A. p53 mutations in lung tumours: relationship to gender and lung DNA adduct levels. Carcinogenesis 1996;17:2201-2205. (Pubitemid 26372059)
60. Ohtake F, Takeyama K-I, Matsumoto T, Kitagawa Y, Yamamoto Y, Nohara T, Tohyama C, Krust A, Mimura J, Chambon P, et al. Modulating of estrogen receptor signalling by association with the activated dioxin receptor. Nature 2003;423:545-550. (Pubitemid 36648579)
61. Wihlén B, Ahmed S, Inzunza J, Matthews J. Estrogen receptor subtype- and promoter-specific modulation of aryl hydrocarbon receptor-dependent transcription. Mol Cancer Res 2009;7:977-986.
62. Spink DC, Eugster HP, Lincoln DW, Schuetz JD, Johnson JA, Kaminsky LS, Gierthy JF. 17 beta-estradiol hydroxylation catalyzed by human cytochrome P450 1A1: a comparison of the activities induced by 2,3,7,8-tetrachlorodibenzo-p- dioxin in MCF-7 cells with those from heterologous expression of the cDNA. Arch Biochem Biophys 1992;293:342-348.
63. Badawi AF, Cavalieri EL, Rogan ER. Role of human cytochrome P450 1A1, 1A2, 1B1, and 3A4 in the 2-, 4-, and 16α-hydroxylation of 17β-estradiol. Metabolism 2001;50:1001-1003. (Pubitemid 32904154)
64. Berge G, ØVrebø S, Hewer A, Phillips DH, Eilertsen E, Haugen A. Role of estrogen receptor in regulation of polycyclic aromatic hydrocarbon metabolic activation in lung. Lung Cancer 2004;45:289-297.
65. Han W, Pentecost BT, Pietropaolo RL, Fasco MJ, Spivack SD. Estrogen receptor a increases the basal and cigarette smoke extract-induced expression of CYP1A1 and CYP1B1, but not GSTP1, in normal human bronchial epithelial cells. Mol Carcinog 2005;44:202-211. (Pubitemid 41552753)
66. Itoh K, Chiba T, Takahashi S, Ishii T, Igarashi K, Katoh Y, Oyake T, Hayashi N, Satoh K, Hatayama M, et al. An Nrf2/small Maf heterodimer mediates the induction of phase II detoxifying enzyme genes through antioxidant response element. Biochem Biophys Res Commun 1997;236:313-322. (Pubitemid 27373291)
67. Jaiswal AK. Regulation of genes encoding NAD(P)H:quinine oxidoreductases. Free Radic Biol Med 2000;29:254-262.
68. Hayes JD, Dinkova-Kostova AT, McMahon M. Cross-talk between transcription factors Ahr and Nrf2: lessons for cancer chemprevention from dioxin. Toxicol Sci 2009;111:199-201.
69. Yeager RL, Reisman SA, Aleksunes LM, Klaassen CD. Introducing the "TCDD inducible AhR-Nrf2 gene battery." Toxicol Sci 2009;111:238-246.
70. McMahon M, Thomas N, Itoh K, Yamamoto M, Hayes JD. Dimerization of substrate adaptors can facilitate cullin-mediated ubiquitylation of proteins by a "tethering" mechanism: a two-site interaction model for the Nrf2-Keap1 conplex. J Biol Chem 2006;281:24756-24768.
71. Reisman SA, Yeager RL, Yamamoto M, Klaassen CD. Increased Nfr2 activation in livers from Keap1-knockdown mice increases expression of cytoprotective genes that detoxify electrophiles more than those that detoxify reactive oxygen species. Toxicol Sci 2009;108:35-47.
72. Ohta T, Iijima K, Miyamoto M, Nakahara I, Tanaka H, Ohtsuji M, Suzuki T, Kobayashi A, Yokota J, Sakiyama T, et al. Loss of Keap1 function activates Nrf2 and provides advantages for lung cancer cell growth. Cancer Res 2008;68:1303-1309. (Pubitemid 351346836)
73. Ramos-Gomez M, Dolan PM, Itoh K, Yamamoto M, Kensler TW. Interactive effects of nfr2 genotype and oltipraz on benzo[a]pyrene-DNA adducts and tumor yield in mice. Carcinogenesis 2003;24:461-467. (Pubitemid 36432641)
74. Hayes JD, McMahon M. NRF2 and KEAP1 mutations: permanent activation of an adaptive response in cancer. Trends Biochem Sci 2009;34:176-188.
75. Iskander K, Gaikwad A, Paquet M, Long DJ, Brayton C, Barrios R, Jaiswal AK. Lower induction of p53 and decreased apoptosis in NQO1-null mice lead to increased sensitivity to chemical-induced skin carcinogenesis. Cancer Res 2005;65:2054-2058. (Pubitemid 40490107)
76. Shen J, Barrios RJ, Jaiswal AK. Inactivation of the quinine oxidoreductases NQO1 and NQO2 strongly elevates the incidence and multiplicity of chemically induced skin tumors. Cancer Res 2010;70:1006-1014.
77. Kim SY, Kim TJ, Lee K-Y. A novel function of peroxiredoxin 1 (Prx-1) in apoptosis signal-regulating kinase (ASK1)-mediated signaling pathway. FEBS Lett 2008;582:1913-1918.
78. Kotlo KU, Yehiely F, Efimova E, Harasty H, Hesabi B, Shchors K, Einat P, Rozen A, Berent E, Deiss LP. Nrf2 is an inhibitor of the Fas pathway as identified by Achilles' Heel Method, a new function-based approach to gene identification. Oncogene 2003;22:797-806. (Pubitemid 36255814)
79. Morito N, Yoh K, Itoh K, Hirayama A, Koyama A, Yamamoto M, Takahashi S. Nrf2 regulates the sensitivity of death receptor signals by affecting intracellular glutathione levels. Oncogene 2003;22:9275-9281. (Pubitemid 38122039)
80. Wikman H, Ruosaari S, Nymark P, Sarhadi VK, Saharinen J, Vanhala E, Karjalainen A, Hollmén J, Knuutila S, Anttila S. Gene expression and copy number profiling suggests the importance of allelic imbalance in 19p in asbestos-associated lung cancer. Oncogene 2007;26:4730-4737. (Pubitemid 47067413)
81. Ruosaari ST, Nymark PE, Aavikko MM, Kettunen E, Knuutila S, Hollmén J, Norppa H, Anttila SL. Aberrations of chromosome 19 in asbestos-associated lung cancer and in asbestos-induced micronuclei of bronchial epithelial cells in vitro. Carcinogenesis 2008;29:913-917. (Pubitemid 351982233)
82. Singh A, Misra V, Thimmulappa RK, Lee H, Ames S, Hoque MO, Herman JG, Baylin SB, Sidransky D, Gabrielson E, et al. Dysfunctional KEAP1-NRF2 interaction in non-small-cell lung cancer. PLoS Med 2008;3:e420.
83. Shibata T, Ohta T, Tong KI, Kokubu A, Odogawa R, Tsuta K, Asamura H, Yamamoto M, Hirohashi S. Cancer related mutations in NRF2 impair its recognition by Keap1-Cul3 E3 ligase and promote malignancy. Proc Natl Acad Sci USA 2008;105:13568-13573.
84. Wang R, An J, Ji F, Jiao H, Sun H, Zhou D. Hypermethylation of the Keap1 gene in human lung cancer cell lines and cancer tissues. Biochem Biophys Res Commun 2008;373:151-154.
85. Smith GBJ, Bend JR, Bedard LL, Reid KR, Petsikas D, Massey TE. Biotransformation of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) in peripheral human lung microsomes. Drug Metab Dispos 2003;31:1134-1141. (Pubitemid 37048285)
86. Dicke KE, Skrlin SM, Murphy SE. Nicotine and 4-(methylnitrosamino)- 1-(3-pyridyl)-1-butanone metabolism by cytochrome P450 2B6. Drug Metab Dispos 2005;33:1760-1764. (Pubitemid 41697258)
87. Hodgson E, Rose RL. The importance of cytochrome P450 2B6 in the human metabolism of environmental chemicals. Pharmacol Ther 2007;113:420-428. (Pubitemid 46149054)
88. Lanza DL, Code E, Crespi CL, Gonzalez F, Yost GS. Specific dehydrogenation of 3-methylindole and epoxidation of naphthalene by recombinant human CYP2F1 expressed in lymphoblastoid cells. Drug Metab Dispos 1999;27:798-803. (Pubitemid 29297777)