Skip to main content

Advertisement

SpringerLink
Log in

Increased CYP1A1 expression in human exfoliated urothelial cells of cigarette smokers compared to non-smokers

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

Abstract

Polycyclic aromatic hydrocarbons, arylamines and nitrosamines, constituents of cigarette smoke, are known inducers of bladder cancer. The biochemical response of the target tissue, the bladder urothelium, following inhalation of cigarette smoke has not been studied so far. We used exfoliated transitional urothelial cells from human urine samples to analyze effects of smoking on induction of the cytochrome P450 enzyme CYP1A1. Samples of 40 subjects, including male and female smokers and non-smokers, were examined. A prerequisite for the immunofluorescence microscopic analysis of the cells was the enrichment of the urothelial cell population. This was achieved by a new method which is based on magnetic cell sorting exploiting specific binding of immobilized Griffonia simplicifolia lectin to the surface of urothelial cells. Immunostaining of the final cell preparation with a monoclonal antibody to CYP1A1 showed that about 6% of the urothelial cells of non-smokers stained positive for CYP1A1. However, this fraction of positive cells was more than 44% of the urothelial cells in samples from cigarette smokers. In spite of the individual variation, the difference was statistically significant. There were no gender-related differences in the portion of CYP1A1 expressing urothelial cells of smokers and non-smokers. In essence, we show for the first time that human urothelial cells respond to cigarette smoking by induction of CYP1A1. The approach opens new fields of mechanistic and biomarker research with respect to the pathogenetic processes of cancer development in the human bladder.

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
Fig. 4

Similar content being viewed by others

References

  • Augustine A, Hebert JR, Kabat GC, Wynder EL (1988) Bladder cancer in relation to cigarette smoking. Cancer Res 8:4405–4408

    Google Scholar 

  • Badawi AF, Mostafa MH (1993) Possible mechanisms of alteration in the capacities of carcinogen metabolizing enzymes during schistosomiasis and their role in bladder cancer induction. J Int Med Res 21:281–305

    PubMed  CAS  Google Scholar 

  • Bock KW, Schrenk D, Förster A, Griese EU, Mörike K, Brockmeier D, Eichelbaum M (1994) The influence of environmental and genetic factors on CYP2D6, CYP1A2 and UDP-glucuronosyltransferases in man using sparteine, caffeine, and paracetamol as probes. Pharmacogenetics 4:209–218

    Article  PubMed  CAS  Google Scholar 

  • Boffetta P, Jourenkova N, Gustavsson P (1997) Cancer risk from occupational and environmental exposure to polycyclic aromatic hydrocarbons. Cancer Causes Control 8:444–472

    Article  PubMed  CAS  Google Scholar 

  • Brand KG (1979) Schistosomiasis–cancer: etiological considerations. A review. Acta Trop 36:203–214

    PubMed  CAS  Google Scholar 

  • Brauers A, Manegold E, Buettner R, Baron JM, Merk HF, Jakse G (2000) Cytochrome P450 isoenzyme mRNA expression pattern in human urinary bladder malignancies and normal urothelium. Cancer Detect Prev 24:356–363

    PubMed  CAS  Google Scholar 

  • Dörrenhaus A, Müller JI, Golka K, Jedrusik P, Schulze H, Föllmann W (2000) Cultures of exfoliated epithelial cells from different locations of the human urinary tract and the renal tubular system. Arch Toxicol 74:618–626

    Article  PubMed  Google Scholar 

  • Flint FF, Schulte BA, Spicer SS (1986) Glycoconjugate with terminal alpha galactose. A property common to basal cells and a subpopulation of columnar cells of numerous epithelia in mouse and rat. Histochemistry 84:387–395

    Article  PubMed  CAS  Google Scholar 

  • Gazdar AF, Czerniak B (2001) Filling the void: urinary markers for bladder cancer risk and diagnosis. J Natl Cancer Inst 93:413–415

    Article  PubMed  CAS  Google Scholar 

  • Golka K, Wiese A, Assennato G, Bolt HM (2004) Occupational exposure and urological cancer. World J Urol 21:382–391

    Article  PubMed  CAS  Google Scholar 

  • Greenlee RT, Murray T, Bolden S, Wingo PA (2000) Cancer statistics, 2000. CA Cancer J Clin 50:7–33

    PubMed  CAS  Google Scholar 

  • Grupp C, John H, Hemprich U, Singer A, Munzel U, Müller GA (2001) Identification of nucleated cells in urine using lectin staining. Am J Kidney Dis 37:84–93

    PubMed  CAS  Google Scholar 

  • Guhe C, Degen GH, Schuhmacher US, Kiefer F, Föllmann W (1996) Drug metabolizing enzyme activities in porcine urinary bladder epithelial cell cultures (PUBEC). Arch Toxicol 70:599–606

    Article  PubMed  CAS  Google Scholar 

  • Hemstreet GP III, Yin S, Ma Z, Bonner RB, Bi W, Rao JY, Zang M, Zheng Q, Bane B, Asal N, Li G, Feng P, Hurst RE, Wang W (2001) Biomarker risk assessment and bladder cancer detection in a cohort exposed to benzidine. J Natl Cancer Inst 93:427–436

    Article  PubMed  Google Scholar 

  • Imaoka S, Yoneda Y, Matsuda T, Degawa M, Fukushima S, Funae Y (1997) Mutagenic activation of urinary bladder carcinogens by CYP4B1 and the presence of CYP4B1 in bladder mucosa. Biochem Pharmacol 54:677–683

    Article  PubMed  CAS  Google Scholar 

  • Imaoka S, Yoneda Y, Sugimoto T, Hiroi T, Yamamoto K, Nakatani T, Funae Y (2000) CYP4B1 is a possible risk factor for bladder cancer in humans. Biochem Biophys Res Commun 277:776–780

    Article  PubMed  CAS  Google Scholar 

  • Iwanari M, Nakajima M, Kizu R, Hayakawa K, Yokoi T (2002) Induction of CYP1A1, CYP1A2, and CYP1B1 mRNAs by nitropolycyclic aromatic hydrocarbons in various human tissue-derived cells: chemical-, cytochrome P450 isoform-, and cell-specific differences. Arch Toxicol 76:287–298

    Article  PubMed  CAS  Google Scholar 

  • Johansson SL, Cohen SM (1997) Epidemiology and etiology of bladder cancer. Semin Surg Oncol 13:291–298

    Article  PubMed  CAS  Google Scholar 

  • Kanitz MH, Swaminathan S, Savage RE Jr (2004) Two-dimensional electrophoretic protein profile analysis following exposure of human uroepithelial cells to occupational bladder carcinogens. Cancer Lett 205:121–131

    Article  PubMed  CAS  Google Scholar 

  • Kirkali Z, Chan T, Manoharan M, Algaba F, Busch C, Cheng L, Kiemeney L, Kriegmair M, Montironi R, Murphy WM, Sesterhenn IA, Tachibana M, Weider J (2005) Bladder cancer: epidemiology, staging and grading, and diagnosis. Urology 66(6 Suppl 1):4–34

    Article  PubMed  Google Scholar 

  • Liou LS (2006) Urothelial cancer biomarkers for detection and surveillance. Urology 67(3 Suppl 1):25–33

    Article  PubMed  Google Scholar 

  • Miller RG (1997) Beyond ANOVA: basics of applied statistics. Chapman & Hall, New York

    Google Scholar 

  • Murphy LA, Goldstein IJ (1977) Five alpha-d-galactopyranosyl-binding isolectins from Bandeiraea simplicifolia seeds. J Biol Chem 252:4739–4742

    PubMed  CAS  Google Scholar 

  • Murray GI, Taylor VE, McKay JA, Weaver RJ, Ewen SW, Melvin WT, Burke MD (1995) Expression of xenobiotic metabolizing enzymes in tumours of the urinary bladder. Int J Exp Pathol 76:271–276

    PubMed  CAS  Google Scholar 

  • Poupko JM, Radomski JL, Hearn WL (1981) Bovine bladder mucosa microsomal cytochrome P-450 and 4-aminobiphenyl N-hydroxylase activity. Cancer Res 41:1306–1310

    PubMed  CAS  Google Scholar 

  • Rivera SP, Saarikoski ST, Hankinson O (2002) Identification of a novel dioxin-inducible cytochrome P450. Mol Pharmacol 61:255–259

    Article  PubMed  CAS  Google Scholar 

  • Romkes M, Chern HD, Lesnick TG, Becich MJ, Persad R, Smith P, Branch RA (1996) Association of low CYP3A activity with p53 mutation and CYP2D6 activity with Rb mutation in human bladder cancer. Carcinogenesis 17:1057–1062

    Article  PubMed  CAS  Google Scholar 

  • Roos PH, Belik R, Föllmann W, Degen GH, Knopf HJ, Bolt HM, Golka K (2006) Expression of cytochrome P450 enzymes CYP1A1, CYP1B1, CYP2E1 and CYP4B1 in cultured transitional cells from specimens of the human urinary tract and from urinary sediments. Arch Toxicol 80:45–52

    Article  PubMed  CAS  Google Scholar 

  • Ross JA, Nelson GB, Wilson KH, Rabinowitz JR, Galati A, Stoner GD, Nesnow S, Mass MJ (1995) Adenomas induced by polycyclic aromatic hydrocarbons in strain A/J mouse lung correlate with time-integrated DNA adduct levels. Cancer Res 55:1039–1044

    PubMed  CAS  Google Scholar 

  • Rylander T, Neve EP, Ingelman-Sundberg M, Oscarson M (2001) Identification and tissue distribution of the novel human cytochrome P450 2S1 (CYP2S1). Biochem Biophys Res Commun 281:529–535

    Article  PubMed  CAS  Google Scholar 

  • Scher HI, Shipley WU, Herr HW (1997) Cancer of the bladder. In: DeVita VT Jr, Hellman S, Rosenberg SA (eds) Cancer: principles and practice of oncology, 5th edn. Lippincott, Philadelphia, pp 1300–1322

    Google Scholar 

  • Schober W, Luch A, Soballa VJ, Raab G, Stegeman JJ, Doehmer J, Jacob J, Seidel A (2006) On the species-specific biotransformation of dibenzo[a,l]pyrene. Chem Biol Interact 161:37–48

    Article  PubMed  CAS  Google Scholar 

  • Sheweita SA, Abu El-Maati MR, El-Shahat FG, Bazeed MA (2001) Changes in the expression of cytochrome P450 2E1 and the activity of carcinogen-metabolizing enzymes in Schistosoma haematobium-infected human bladder tissues. Toxicology 162:43–52

    Article  PubMed  CAS  Google Scholar 

  • Shimada T, Oda Y, Gillam EM, Guengerich FP, Inoue K (2001) Metabolic activation of polycyclic aromatic hydrocarbons and other procarcinogens by cytochromes P450 1A1 and P450 1B1 allelic variants and other human cytochromes P450 in Salmonella typhimurium NM2009. Drug Metab Dispos 29:1176–1182

    PubMed  CAS  Google Scholar 

  • Vanderslice RR, Boyd JA, Eling TE, Philpot RM (1985) The cytochrome P-450 monooxygenase system of rabbit bladder mucosa: enzyme components and isozyme 5-dependent metabolism of 2-aminofluorene. Cancer Res 45:5851–5858

    PubMed  CAS  Google Scholar 

  • Villard PH, Herber R, Seree EM, Attolini L, Magdalou J, Lacarelle B (1998) Effect of cigarette smoke on UDP-glucuronosyltransferase activity and cytochrome P450 content in liver, lung and kidney microsomes in mice. Pharmacol Toxicol 82:74–79

    Article  PubMed  CAS  Google Scholar 

  • Vineis P, Pirastu R (1997) Aromatic amines and cancer. Cancer Causes Control 8:346–355

    Article  PubMed  CAS  Google Scholar 

  • Wilson JY, Cooke SR, Moore MJ, Martineau D, Mikaelian I, Metner DA, Lockhart WL, Stegeman JJ (2005) Systemic effects of arctic pollutants in beluga whales indicated by CYP1A1 expression. Environ Health Perspect 113:1594–1599

    Article  PubMed  CAS  Google Scholar 

  • Wolf A, Kutz A, Plöttner S, Behm C, Bolt HM, Föllmann W, Kuhlmann J (2005) The effect of benzo(a)pyrene on porcine urinary bladder epithelial cells analyzed for the expression of selected genes and cellular toxicological endpoints. Toxicology 207:255–269

    Article  PubMed  CAS  Google Scholar 

  • Ying-Hao S, Qing Y, Lin-Hui W, Li G, Rong T, Kang Y, Chuan-Liang X, Song-Xi Q, Yao L, Yi X, Yu-Ming M (2002) Monitoring gene expression profile changes in bladder transitional cell carcinoma using cDNA microarray. Urol Oncol 7:207–212

    Article  PubMed  Google Scholar 

  • Yu MC, Skipper PL, Tannenbaum SR, Chan KK, Ross RK (2002) Arylamine exposures and bladder cancer risk. Mutat Res 506–507:21–28

    PubMed  Google Scholar 

  • Zeegers MP, Kellen E, Buntinx F, van den Brandt PA (2004) The association between smoking, beverage consumption, diet and bladder cancer: a systematic literature review. World J Urol 21:392–401

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

We thank Hermann M. Bolt and Gisela H. Degen (IfADo, Dortmund) for most valuable discussions. The authors wish to express thanks to all volunteers who provided urine samples as a prerequisite for this study. We would also like to thank the Thermo Shandon company (Dreieich, Germany), particularly Mr. Joachim Obst, for kind support of our investigations.

Author information

Authors and Affiliations

  1. Institute for Occupational Physiology at the University Dortmund, Ardeystr 67, 44139, Dortmund, Germany

    Angelika Dörrenhaus, Tina Müller & Peter H. Roos

  2. Department of Statistics, Mathematical Statistics with Applications in Biometrics, University Dortmund, Vogelpothsweg 87, 44227, Dortmund, Germany

    Tina Müller

Authors
  1. Angelika Dörrenhaus
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Tina Müller
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Peter H. Roos
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Peter H. Roos.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Dörrenhaus, A., Müller, T. & Roos, P.H. Increased CYP1A1 expression in human exfoliated urothelial cells of cigarette smokers compared to non-smokers. Arch Toxicol 81, 19–25 (2007). https://doi.org/10.1007/s00204-006-0134-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00204-006-0134-9

Keywords

Search

Navigation