Springer Nature is making SARS-CoV-2 and COVID-19 research free. View research | View latest news | Sign up for updates

Immunohistochemical localization of cytochrome P450 2E1 in human pulmonary carcinoma and normal bronchial tissue


Cytochrome P450 2E1 (CYP2E1) is a major xenobiotic-metabolizing enzyme but data concerning its extrahepatic expression are few. CYP2E1 can metabolically activate many procarcinogens and therefore its presence in the lung might play a role in bioactivation of procarcinogens, so we studied the expression and localization of CYP2E1 in primary pulmonary carcinomas and surrounding normal bronchial tissue from 28 patients. Seromucous glands showed expression of CYP2E1 in 19 and bronchial epithelium in 18 of the 28 samples of normal bronchial tissue. Thirteen of the corresponding cases of primary pulmonary carcinoma showed staining for CYP2E1. In 11 of these 13 cases, CYP2E1 was also present in normal bronchial tissue. There was no statistically significant difference in the expression of CYP2E1 between adenocarcinomas and squamous cell carcinomas. No association was observed between the expression of CYP2E1 in tumour tissue and normal bronchial tissue. However, there was a significant correlation between the expression of CYP2E1 in seromucous glands and bronchial epithelium (r=0.61, P<0.01) of normal tissue. We conclude that CYP2E1 can be present in both normal and neoplastic bronchial tissue.

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


  1. 1.

    Bend JR, Serabjit-Singh CJ, Philpot RM (1985) The pulmonary uptake, accumulation, and metabolism of xenobiotics. Annu Rev Pharmacol Toxicol 25:97–125

  2. 2.

    Cohen GM, Gibby EM, Mehta R (1981) Routes of conjugation in normal and cancerous tissue from human lung. Nature 291:662–664

  3. 3.

    Czerwinski M, McLemore TL, Gelboin HV, Gonzalez FJ (1994) Quantification of CYP2B7, CYP4B1, and CYPOR messenger RNAs in normal lung and lung tumours. Cancer Res 54:1085–1091

  4. 4.

    Fritz P, Mueller J, Wegner G, Braun U, Grau A, Tuczek HV, Moessner E, Schenk R (1985) Immunohistochemie: theoretische Möglichkeiten, praktische Anwendungen. Zentralbl Allg Pathol 130:187–193

  5. 5.

    Fritz P, Behrle E, Beaune P, Eichelbaum M, Kroemer HK (1993) Differential expression of drug metabolizing enzymes in primary and secondary liver neoplasm: immunohistochemical characterization of cytochrome P4503A and glutathione-S-transferase. Histochemistry 99:443–451

  6. 6.

    Guengerich FP, Kim D-H, Iwasaki M (1991) Role of human cytochrome P-450 IIE1 in the oxidation of many low molecular weight cancer suspects. Chem Res Toxicol 4:168–179

  7. 7.

    Hsu SM, Soban E (1982) Color modification of diaminobenzidine (DAB) precipitation by metallic ions and its application for double immunocytochemistry. J Histochem Cytochem 30:1079–1082

  8. 8.

    Hsu SM, Raine L, Fanger H (1981) The use of anti-avidin antibody and avidin-biotin-complex in immunoperoxidase techniques. Am J Clin Pathol 75:816–821

  9. 9.

    Ingelman-Sundberg M, Johansson I, Yin H, Terelius Y, Eliasson E, Clot P, Albano E (1993) Ethanol-inducible cytochrome P4502E1: genetic polymorphism, regulation, and possible role in the etiology of alcohol-induced liver disease. Alcohol 10:447–452

  10. 10.

    Kikkawa Y (1992) Diverse role of pulmonary cytochrome P-450 monooxygenase. Lab Invest 67:535–539

  11. 11.

    Kivistö KT, Fritz P, Linder A, Friedel G, Beaune P, Kroemer HK (1995) Immunohistochemical localization of cytochrome P450 3A in human pulmonary carcinomas and normal bronchial tissue. Histochemistry 103:25–29

  12. 12.

    Koop DR (1992) Oxidative and reductive metabolism by cytochrome P450 2E1. FASEB J 6:724–730

  13. 13.

    Krishna DR, Klotz U (1994) Extrahepatic metabolism of drugs in humans. Clin Pharmacokinet 26:144–160

  14. 14.

    McLemore TL, Adelberg S, Liu MC, McMahon NA, Yu SJ, Hubbard WC, Czerwinski M, Wood TG, Storeng R, Lubet RA, Eggleston JC, Boyd MR, Hines RN (1990) Expression of CYP1A1 gene in patients with lung cancer: evidence for cigarette smoke-induced gene expression in normal lung tissue and for altered gene regulation in primary pulmonary carcinomas. J Natl Cancer Inst 82:1333–1339

  15. 15.

    Toussaint C, Albin N, Massaad L, Grunenwald D, Parise O, Morizet J, Gouyette A, Ghabot GG (1993) Main drug-and carcinogen-metabolizing enzyme systems in human non-small cell lung cancer and peritumoral tissues. Cancer Res 53:4608–4612

  16. 16.

    Voigt JM, Kawabata TT, Burke JP, Martin MV, Guengerich FP, Baron J (1990) In situ localization and distribution of xenobiotic-activating enzymes and aryl hydrocarbon hydroxylase activity in lungs of untreated rats. Mol Pharmacol 37:182–191

  17. 17.

    Wheeler CW, Wrighton SA, Guenthner TM (1992) Detection of human lung cytochromes P450 that are immunochemically related to cytochrome P450IIE1 and cytochrome P450IIIA. Biochem Pharmacol 44:183–186

  18. 18.

    Wössner R, Toomes H, Fritz P, Linder A, Dierkesmann RE, Behrle E, Wicherek C (1994) Immunohistochemical demonstration of glycoprotein 170 and glutathione S-transferase isoenzymes in normal and neoplastic bronchial tissue. Onkologie 17:28–34

Download references

Author information

Correspondence to K. Kivistö.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Kivistö, K., Kroemer, H., Linder, A. et al. Immunohistochemical localization of cytochrome P450 2E1 in human pulmonary carcinoma and normal bronchial tissue. Vichows Archiv A Pathol Anat 426, 243–247 (1995).

Download citation

Key words

  • CYP2E1
  • Immunohistochemistry
  • Pulmonary carcinoma