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Changes in the expression of cytochrome P450 isozymes and related carcinogen metabolizing enzyme activities in Schistosoma mansoni-infected mice

Published online by Cambridge University Press:  12 April 2024

S.A. Sheweita ,
J. Mubark ,
M.J. Doenhoff ,
M.H. Mostafa ,
G.P. Margison ,
P.J. O'Connor  and
R.H. Elder
S.A. Sheweita*
Affiliation:
Department of Bioscience and Technology, Institute of Graduate Studies and Research, Alexandria University, 163 Horreya Ave., PO Box 832, Alexandria, Egypt
J. Mubark
Affiliation:
School of Biological Sciences, University of Wales, Bangor, UK
M.J. Doenhoff
Affiliation:
School of Biological Sciences, University of Wales, Bangor, UK
M.H. Mostafa
Affiliation:
Department of Environmental Studies, Institute of Graduate Studies and Research, Alexandria University, Egypt
G.P. Margison
Affiliation:
CRC Carcinogenesis Group, Paterson Institute for Cancer Research, Christie Hospital (NHS) Trust, Manchester, UK
P.J. O'Connor
Affiliation:
CRC Carcinogenesis Group, Paterson Institute for Cancer Research, Christie Hospital (NHS) Trust, Manchester, UK
R.H. Elder
Affiliation:
CRC Carcinogenesis Group, Paterson Institute for Cancer Research, Christie Hospital (NHS) Trust, Manchester, UK
*
*Fax: (203) 428 5792 Email: [email protected]
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Abstract

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Mixed-function oxidase enzymes metabolize most xenobiotic agents. Western blotting was used to investigate the effect of Schistosoma mansoni infection on the expression of various cytochrome P450 (CYP) isozymes and specific enzyme assays to study related metabolic functions in mouse liver microsomes. Male BK-TO mice were infected with 200 cercariae per mouse and their livers were assayed at 6, 15, 30 and 45 days post-infection (p.i.) and compared with appropriately matched controls. The expression of each of the CYP isozymes (1A1, 2B1/2, 2C6, and 4A) was either unaffected or transiently increased up to 30 days post-infection. By 45 days, a significant loss of signal was observed, particularly for CYP 1A1 and 2B1/2 where no signal could be detected. Evidence supporting these findings was obtained from enzyme assays specific for particular CYP isozymes. The activity of ethoxyresorufin O-deethylase (CYP 1A1) was reduced by 97% and that of pentoxyresorufin O-depentylase (CYP 2B1/2) by 96% at 45 days p.i. Similarly, the activity of ethoxycoumarin hydroxylase was progressively reduced over the period under study. It is believed that N-nitrosamines are activated principally by N-nitrosodimethylamine N-demethylase I which was significantly increased at both 30 and 45 days p.i. To further investigate metabolic competency following S. mansoni infection, the in vitro binding of benzo(a)pyrene metabolites to DNA was measured, using isolated liver microsomes to activate benzo(a)pyrene. Benzo(a)pyrene-DNA adduct formation was markedly increased at 6, 15 and 30 days with a maximum at 15 days, but decreased at 45 days p.i. It was concluded that S. mansoni infection changes the expression of different CYP isozymes and also the activity of phase I drug-metabolizing enzymes at different periods of infection and may thus change the liver's capacity to activate or detoxify many endogenous and exogenous compounds. Such alterations may also change the therapeutic actions of drugs that are primarily metabolized by the P450 system, when administered to patients with schistosomiasis.

Type
Review Article
Information
Journal of Helminthology , Volume 76 , Issue 1 , March 2002 , pp. 71 - 78
Copyright
Copyright © Cambridge University Press 2002

References

Allis, J.W., Brown, B.L., Simmons, J.E., Hatch, G.E., McDonald, A. & House, D.E. (1996) Methanol potentiation of carbon tetrachloride hepatotoxicity: the central role of cytochrome P450. Toxicology 16, 131–140.CrossRefGoogle Scholar
Al-Shukri, S., Alwan, M.H., Nayef, L.H. & Rahman, A.A. (1987) Bilharziasis in malignant tumors of the urinary bladder. British Journal of Urology 59, 59–62.CrossRefGoogle ScholarPubMed
Arcos, J., Davies, D.L., Brown, C.E. & Argus, M.E. (1977) Repressible and inducible enzymatic forms of DMN-demethylase. Zeitschrift für Krebsforschung und Klinische Onkologie 89, 181–199.CrossRefGoogle Scholar
Ashurst, S.T. & Cohen, G.L. (1981) The formation and persistence of benzo(a)pyrene metabolite-deoxyribo-nucleoside adducts in rat skin in vivo . International Journal of Cancer 28, 387–392.CrossRefGoogle ScholarPubMed
Badawi, A.F., Cooper, D.P., Mostafa, M.H., Doenhoff, M.J., Probert, A., Fallon, P., Cooper, R. & O'Connor, P.J. (1993) Promutagenic methylation damage in liver DNA of mice infected with Schistosoma mansoni . Carcinogenesis 14, 653–657.CrossRefGoogle ScholarPubMed
Bartsch, H. & Montesano, R. (1984) Relevance of nitrosamines to human cancer. Carcinogenesis 5, 1381–1393.CrossRefGoogle ScholarPubMed
Bjelogrlic, N., Peng, R., Park, S.S., Gelboin, H.V., Honkakoski, P., Pelkonen, O. & Vahakangas, K. (1993) Involvement of P4501A1 in benzo(a)pyrene but not in benzo(a)pyrene-7,8-dihydrodiol activation by 3-methylcholanthrene-induced mouse liver microsomes.. Pharmacology and Toxicology 73, 319–324.CrossRefGoogle Scholar
Burke, M.D., Thompson, S., Elcombe, C.R., Halpert, J., Haaparanta, T. & Mayer, R.T. (1985) Ethoxy-, pentoxy- and benzyloxyphenoxazones and homologues: a series of substrates to distinguish between different induced cytochromes P450. Biochemical Pharmacology 34, 3337–3345.CrossRefGoogle Scholar
Butler, M.A., Iwasaki, M., Guengerich, F.P. & Kadlubar, F.F. (1989) Human cytochrome P450 (P450 1A2), the phenacetin O-deethylase, is primarily responsible for the hepatic 3-demethylation of caffeine and N-oxidation of carcinogenic arylamines. Proceeding of the National Academy of Sciences, USA 86, 7696–7700.CrossRefGoogle Scholar
Camus, A.M., Geneste, O., Honkakoski, P., Bereziat, J.C., Henderson, C.J., Wollf, C.R., Bartsch, H. & Lang, M.A. (1993) High variability of metabolism among individuals: role of cytochrome P450 2A6 and 2E1 in the dealkylation of N-nitrosodimethylamine and N- nitrosodiethylamine in mice and humans.. Molecular Carcinogenesis 7, 268–275.CrossRefGoogle Scholar
Cheever, A.W. (1978) Schistosomiasis and neoplasm. Journal of the National Cancer Institute 61, 13–18.CrossRefGoogle Scholar
Conney, A.H. (1982) Induction of microsomal enzymes by foreign chemicals and carcinogenesis by polycyclic aromatic hydrocarbons. Cancer Research 42, 4875–4917.Google ScholarPubMed
Cooper, D.P., Yoa, G.F., Qu, Y.H. & O'Connor, P.J. (1991) DNA methylation in individuals at high risk for stomach cancer. British Journal of Cancer 13, 65–71.Google Scholar
Delmas, V., Daug, M.C., Davody, A.P., Coulaud, J.P. & Moulonguet, A. (1986) Carcinoma of the bladder in urinary schistosomiasis. Annals of Urology 20, 213–217.Google Scholar
El-Mouelhi, M., Black, M. & Phillips, M. (1987) Hepatic cyctochrome P450 system in experimental hepatosplenic schistosomiasis. Presence of an artifact in spectrophotometric analysis. Biochemical Pharmacology 36, 2621–2626.CrossRefGoogle Scholar
Everson, R.B., Randerath, E., Santella, R.M., Cefalo, R.C., Avitts, T.A. & Randerath, K. (1986) Detection of smoking-related covalent DNA adducts in human placenta. Science 231, 54–57.CrossRefGoogle ScholarPubMed
Gelboin, H.V. (1980) Benzo(a)pyrene metabolism, activation and carcinogenesis: role and regulation of mixed-function oxidases and related enzymes. Physiological Reviews 60, 1107–1166.CrossRefGoogle Scholar
Gonzalez, F.J. & Gelboin, H.V. (1994) Role of human cytochrome P-450 in the metabolic activation of chemical carcinogens and toxins. Drug Metabolism Reviews 26, 165–171.CrossRefGoogle ScholarPubMed
Gooderham, N.J. & Mannering, G.J. (1985) Depression of the hepatic cytochrome P450 monooxygenase system by treatment of mice with the anti-neoplastic agent, 5-azacytidine. Cancer Research 45, 1569–1572.Google Scholar
Greenle, W.F. & Poland, A. (1978) An improved assay of 7-ethoxycoumarin O-deethylase activity: induction of hepatic enzyme activity in C57BL/6J and DBA/2J mice by phenobarbital, 3-methylcholantherene and 2,3,7,8-tetrachlorodibenzo-p-dioxin. Journal of Pharmacology and Experimental Therapeutics 205, 596–605.Google Scholar
Guengerich, F.P. (1991) Oxidation of toxic and carcinogenic chemicals by human cytochrome P-450 enzymes. Chemical Research Toxicology 4, 391–407.CrossRefGoogle ScholarPubMed
Habib, S.L., Sheweita, S.A., Awad, A., Mashaal, N., Soliman, A. & Mostafa, M.H. (1996) Influence of Schistosoma mansoni infection on carcinogen-metaboliz-ing capacities and in vitro aflatoxin Ba metabolism in human liver.. Oncology Reports 3, 769–773.Google Scholar
Hammons, G.J., Guengerich, F.P., Weis, C.C., Beland, F.A. & Kadlubar, F.F. (1985) Metabolic oxidation of carcinogenic arylamines by rat, dog and human hepatic microsomes and by purified flavin-containing and cytochrome P450 monooxygenases. Cancer Research 45, 3578–3585.Google Scholar
Hanioka, N., Omae, E., Nishimura, T., Jinno, H., Onodera, S., Yoda, R. & Ando, M. (1996) Interaction of 2,4,4′-trichloro-2′-hydroxydiphenyl ether with microsomal cytochrome P450-dependent monooxygenases in rat liver. Chemosphere 33, 265–276.CrossRefGoogle ScholarPubMed
Harris, C.C., Vahakangas, K., Newman, M.J., Trivers, G.E., Shamsuddin, A.K., Sinopoli, N.T., Mann, D.L. & Wright, W.E. (1985) Detection of benzo(a)pyrene diolepoxide in serum from coke oven workers. Proceedings of the National Academy of Sciences, USA 82, 6672–6676.CrossRefGoogle Scholar
Hashem, M. & Boutros, K. (1961) The influence of bilharzial infection on the carcinogenesis of the bladder. An experimental study. Journal of the Egyptian Medical Association 44, 598–606.Google ScholarPubMed
Hasler, J.A., Siwela, A.H., Nyathi, C.B. & Chetsanga, C.J. (1986) The effect of schistosomiasis on the activation of aflatoxin B1 . Research Communications in Pathology and Pharmacology 51, 421–423.Google ScholarPubMed
Hill, M.J. (1988) N-nitroso compounds and human cancer, pp. 90–102 in Hill, M.J. (Ed.) Nitrosamine toxicology and microbiology. Chichester, Ellis Horwood.Google Scholar
Ishii, A., Matsuoka, H., Aji, T., Ohta, N., Arimoto, S., Wataya, Y. & Hayatsu, H. (1994) Parasite infection and cancer: with special emphasis on Schistosoma japonicum infection (Trematoda). A review. Mutation Research 305, 273–281.CrossRefGoogle ScholarPubMed
Ishizaki, H., Brady, J.F., Ning, S.M. & Yang, C.S. (1990) Effect of phenethyl isothiocyanate on microsomal N-nitrosodimethylamine metabolism and other monooxygenase activities. Xenobiotica 3, 255–264.CrossRefGoogle Scholar
Jerina, D.M., Yagi, H., Thakker, D.R., Karley, J.M., Mak, H.D., Boyd, D.R., Gadaginamath, G., Wood, A.W., Buening, M., Chang, R.L., Levin, W. & Conney, A.H. (1979) Stereoselective metabolic activation of polycyclic aromatic hydrocarbons. Advanced Pharmacology and Therapeutics 9, 53–62.Google Scholar
Kakizoe, Y. (1985) The influence of Schistosoma mansoni infection on carcinogenesis of mouse livers initiated by N-2-fluorenylacetamide. Kurume Medical Journal 32, 169–178.CrossRefGoogle ScholarPubMed
Kim, S.Y., Chung, J.H., Kang, K.W., Joe, C.O. & Park, K.H. (1992) Relationship between activities of cytochrome P450 monooxygenases in human placental microsomes and binding of benzo(a)pyrene metabolites to calf thymus DNA. Drug Chemistry and Toxicology 15, 313–327.CrossRefGoogle ScholarPubMed
Lake, B.G. (1999) Coumarin metabolism, toxicity and carcinogenicity: relevance for human risk assessment. Food Chemistry and Toxicology 37, 423–453.CrossRefGoogle ScholarPubMed
Lake, B.G., Gray, T.J., Evans, J.G., Lewis, D.F., Beamand, J.A. & Hue, K.L. (1989) Studies on the mechanism of coumarin-induced toxicity in rat hepatocytes: comparison with dihydrocoumarin and other coumarin metabolites. Toxicology and Applied Pharmacology 97, 311–323.CrossRefGoogle ScholarPubMed
Lake, B.G., Charzat, C., Tredger, J.M., Renwick, A.B., Beamand, J.A. & Price, R.J. (1996) Induction of cytochrome P450 isoenzymes in cultured precision-cut rat and human liver slices. Xenobiotica 3, 297–306.CrossRefGoogle Scholar
Lijinsky, W., Conrad, E. & Van De Bogart, R. (1972) Nitrosoamines formed by drug/nitrite interactions. Nature 239, 165–174.CrossRefGoogle Scholar
Lowry, O.H., Rosbrough, N.J., Farr, A.L. & Randall, R.J. (1951) Protein measurement with the Folin phenol reagent. Journal of Biological Chemistry 193, 265–275.CrossRefGoogle ScholarPubMed
Manchester, D.K., Bowman, E.D., Parker, N.B., Caporaso, N.E. & Weston, A. (1992) Determinants of polycyclic aromatic hydrocarbons-DNA adducts in human placenta. Cancer Research 52, 1499–1503.Google Scholar
Mclean, A.E. & Day, P.A. (1974) The use of new methods to measure the effect of diet and inducers of microsomal enzyme synthesis on cytochrome P-450 in liver homogenates, and on metabolism of dimethylnitrosamine. Biochemical Pharmacology 23, 1173–1180.CrossRefGoogle Scholar
Miyasato, M. (1984) Experimental study of the influence of Schistosoma japonicum infection on carcinogenesis of mouse liver treated with N-2-fluorenylacetamide (2-FAA). Japanese Journal of Parasitology 33, 41–48.Google Scholar
Morse, M.A., Zu, H., Galati, A.J., Schmidt, C.J. & Stoner, G.D. (1993) Dose-related inhibition by dietary phenethyl isothiocyanate of esophageal tumorigenesis and DNA methylation induced by N-nitrosomethylbenzylamine in rats. Cancer Letters 72, 103–110.CrossRefGoogle ScholarPubMed
Mostafa, M.H. & Sheweita, S.A. (1992) Modification of the oxidative N-demethylation of dimethylnitrosamine by various anti-inflammatory drugs. Ramazzini Newsletters 2, 15–22.Google Scholar
Nash, T. (1953) The calorimetric estimation of formaldehyde by means of Hantzsch reactions. Biochemical Journal 55, 416–421.CrossRefGoogle Scholar
Pohl, R.J. & Fouts, J.R. (1980) A rapid and sensitive method for assaying the metabolism of 7-ethoxyresorufin by microsomal subcellular fractions. Analytical Biochemistry 107, 150–155.CrossRefGoogle Scholar
Preussmann, P. (1984) Occurrence and exposure to N-nitroso compounds and precursors, pp. 3–15 in O'Neil, I.K., Von Borstll, R.C., Miller, C.T., Long, J. & Bartsch, H. (Eds) N-nitroso compounds: occurrence, biological effects and relevance to human cancer. International Agency for Research on Cancer, IARC Sci, Lyon.Google Scholar
Savela, K. & Hemminki, K. (1991) DNA adducts in lymphocytes and granulocytes of smokers and nonsmokers detected by the 32P-postlabeling assay. Carcinogenesis 12, 503–508.CrossRefGoogle Scholar
Sheweita, S.A. (2000) Drug-metabolizing enzymes: mechanisms and functions. Current Drug Metabolism 1, 107–132.CrossRefGoogle ScholarPubMed
Sheweita, S.A. & Mostafa, M.H. (1995) Recovery of the hepatic carcinogen-metabolizing capacity in schistosome-infected mice after treatment with the antischistosomal praziquantel. Oncology Reports 2, 155–159.Google ScholarPubMed
Sheweita, S.A. & Mostafa, M.H. (1996) N-nitroso compounds induce changes in carcinogen-metabolizing enzymes. Cancer Letters 106, 243–249.CrossRefGoogle ScholarPubMed
Sheweita, S.A., Habib, S.L. & Mostafa, M.H. (1997) Schistosomiasis induced changes in glutathione levels and glutathione reductase/glutathione S-transferase activities in human liver. Biomedical Letters 56, 119–127.Google Scholar
Sheweita, S.A., Mangoura, S.A. & El-Shemi, A.G. (1998) Different levels of Schistosoma mansoni induce changes in drug-metabolizing enzymes. Journal of Helminthology 72, 71–77.CrossRefGoogle ScholarPubMed
Siwela, A.H., Nyathi, C.B., Chetsanga, C.J. & Hasler, J.A. (1990) The effect of schistosomiasis on the covalent binding of 2-acetylaminofluorene to mouse liver macromolecules in vivo and in vitro . Biochemical Pharmacology 40, 379–382.CrossRefGoogle ScholarPubMed
Smithers, S.R. & Terry, R.J. (1965) The infection of laboratory hosts with cercariae of Schistosoma mansoni and the recovery of adult worms. Parasitology 55, 695–700.CrossRefGoogle ScholarPubMed
Thompson, T., Watkins, J. & Gergus, Z. (1982) Effect of microsomal enzyme inducers on the soluble enzymes of phase II biotransformation. Toxicology and Applied Pharmacology 66, 400–408.CrossRefGoogle ScholarPubMed
Umbenhauer, D., Wild, C.P., Montesano, R., Saffhill, R., Boyle, J.M., Huh, N., Kirstein, U., Thomale, J., Rajewski, M.F. & Lu, S.H. (1985) O 6-Methyldeoxyguanosine in oesophageal DNA among individuals at high risk of oesophageal cancer. International Journal of Cancer 36, 661–665.CrossRefGoogle ScholarPubMed
Vahakangas, K., Raunio, H., Pasanen, M., Sivonen, P., Park, S.-S., Gelboin, H.V. & Pelkonen, O. (1989) Comparison of the formation of benzo(a)pyrene diolepoxide-DNA adducts in vitro by rat and human microsomes: evidence for the involvement of P450 1A1 and P450 1A2. Journal of Biochemical Toxicology 4, 79–83.CrossRefGoogle Scholar
Venkatesan, N., Arcos, J.C. & Argus, M.F. (1968) Differential effect of polycyclic hydrocarbons on the demethylation of the carcinogen dimethylnitrosamine by rat tissues. Life Science 7, 1111–1118.CrossRefGoogle ScholarPubMed
Wattenberg, L.W. (1987) Inhibitory effects of benzyl isothiocyanate administered shortly before diethylnitrosamine or benzo(a)pyrene on pulmonary and forestomach neoplasia in A/J mice. Carcinogenesis 12, 1971–1973.CrossRefGoogle Scholar
World Health Organization (1985) The control of schistosomiasis. Report of WHO Expert Committee. Technical Report Series No. 728, WHO, Geneva.Google Scholar
World Health Organization (1986) The epidemiological association between Schistosoma haematobium infection and bladder cancer. Report of WHO Expert Committee. Technical Report Series WHO/Schist/86. WHO/CAN/86.1, Geneva.Google Scholar
Yang, C.S., Yoo, J.S., Ishizaki, H. & Hong, J.Y. (1990) Cytochrome P450IIE1: roles in nitrosamine metabolism and mechanisms of regulation. Drug Metabolism Reviews 22 (2–3), 147–159.CrossRefGoogle ScholarPubMed
Yoo, J.S., Ishizaki, H. & Yang, C.S. (1990) Roles of cytochrome P450IIE1 in the dealkylation and denitrosation of N-nitrosodimethylamine and N-nitrosodiethylamine in rat liver microsomes. Carcinogenesis 12, 2239–2243.CrossRefGoogle Scholar
Yoo, J.S.H., Guengerich, F.P. & Yang, C.S. (1988) Metabolism of N-nitrosodialkylamines by human liver microsomes. Cancer Research 88, 1499–1504.Google Scholar
Zhuo, X., Gu, J., Zhang, Q.Y., Spink, D.C., Kaminsky, L.S. & Ding, X. (1999) Biotransformation of coumarin by rodent and human cytochromes P-450: metabolic basis of tissue-selective toxicity in olfactory mucosa of rats and mice. Journal of Pharmacology and Experimental Therapeutics 288, 463–471.Google ScholarPubMed