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Prognostic risk factor of the development of pathological processes based on polymorphism of xenobiotic metabolism enzymes

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Abstract

Analysis of the literature concerning the possibilities of predicting the risk of the development of pathological processes based on the polymorphism of the enzymes of metabolism and detoxification of xenobiotics (EMDX)—cytochrome P-450, glutathione S-transferase, epoxide hydrolase, sulfotransferase, N-acetyltransferase, and UDP-glucuronosyltransferase—was made. The analysis showed that individual predisposition to one or another disease due to the action of xenobiotics depends on the genetically or phenotypically determined state and the polymorphism of the EMDX system. A comparison of the prognostic methods of intravital assessment of the metabolic status of the organism was made, and their advantages and shortcomings were considered. The study of the individual status of the EMDX system is acquiring general medical importance for solving the tasks of the early prognosis, diagnosis, prevention, and chemotherapy of different diseases associated with congenital or acquired defects of the metabolic status of the body.

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References

  1. Lakin, K.M. and Krylov, Yu.F.,Biotransformatsiya lekarstvennykh veshchestv (Biotransformation of Medicinal Substances), Moscow: Meditsina, 1981.

    Google Scholar 

  2. Kholodov, L.E. and Yakovlev, V.P.,Klinicheskaya farmakologiya (Clinical Pharmacology), Moscow: Meditsina, 1985.

    Google Scholar 

  3. Saprin, A.N., The Enzymes of Metabolism and Detoxification of Xenobiotics,Usp. Biol. Khim., 1991, vol. 32, p. 146.

    Google Scholar 

  4. Piruzyan, L.A., Pharmacological Methology,Izv. Akad. Nauk SSSR, Ser. Biol., 1990, no. 2, p. 302.

    Google Scholar 

  5. Piruzyan, L.A. and Mikhailovskii, E.M., Metabolic Equality of Donor and Recipient as a Criterion of their Histocompatibility and The Condition for Performing Transplantation.Fiziol. Chel., 1997, vol. 23, no. 6, p. 115.

    Google Scholar 

  6. Piruzyan, L.A. and Mikhailovskii, E.M., Theoretical Substantiation of the Experimental Data on Transplant Survival in Donor and Recipient.Fiziol. Chel., 1998, vol. 24, no. 1, p. 70.

    Google Scholar 

  7. Ames, B.N., McCenn, J., and Yanusaki, E.,Salmonella typhimurium mutants TA 1535, TA 1537, TA 1538, TA 98, and TA 100 as Tools for Investigation of Mutagenetically Reactive Metabolites.Mutat. Res., 1975, vol. 31, p. 347.

    PubMed  CAS  Google Scholar 

  8. Bentley, P., Oesch, F., and Glatt, H., Roles of the Various Phase-11 Enzymes in Benz[a]pyrene Metabolically Activated Mutagenicity,Arch. Toxicol., 1977, vol. 39, p. 65.

    Article  PubMed  CAS  Google Scholar 

  9. Thekker, D.R., Yagi, H., Lu, A.Y.H.,et al., 7,8-Dihydrodiol-9,10-Epoxide Benz[a]pyrene Is Not Inactivated by Microsomal Epoxide Hydrolase,Proc. Natl. Acad. Sci. USA, 1976, vol. 73, p. 3381.

    Article  Google Scholar 

  10. Glatt, H. and Oesch, F., Structural and Metabolic Parameters Governing the Mutagenicity of Polycyclic Aromatic Hydrocarbons inChemical Mutagenesis, Serres, F.J., Ed., New York: Plenum, 1986, p. 77.

    Google Scholar 

  11. Glatt, H.R., Cooper, C.S., Grover, P.L.,et al., Effectiveness of Various Purified Enzymes in the Inactivation of Benz[a]anthracene Oxides,Science, 1982, vol. 215, p. 1507.

    Article  PubMed  CAS  Google Scholar 

  12. Glatt, H.R., Friedberg, P., and Grover, P.L., Effectiveness of Glutathione S-Transferases and Epoxide Hydrolases in the Inactivation of Benzpyrene Mutagenic Metabolites,Cancer Res., 1983, vol. 43, p. 5713.

    PubMed  CAS  Google Scholar 

  13. Oesch, F., Bentley, P., and Glatt, H.R., Metabolism of Benz[α]pyrene to Mutagens forSalmonella thyphimurium by Liver Microsomes and from Rodents,Int. J. Cancer, 1976, vol. 18, p. 448.

    Article  PubMed  CAS  Google Scholar 

  14. Oesch, F., Antimutagenesis by Shift in Monooxygenase Isoenzymes and Induction of Epoxide Hydrolase,Mutat. Res., 1988, vol. 202, p. 335.

    PubMed  CAS  Google Scholar 

  15. Gauntier, J.C., Lecoeter, S., Cosme, L.,et al., Contribution of Human Cytochrome P-450 to Benz[a]pyrene and Benz[a]-7,8-Dihydrodiol Metabolites,Pharmacogenetics, 1996, vol. 6, p. 489.

    Article  Google Scholar 

  16. Shou, M., Korzekwa, K.R., Crespi, C.L.,et al., The Role of 12 cDNA-expressed Human, Rodent, and Rabbit Cytochrome P-450 in the Metabolism of Benz[a]pyrene,Mol. Carcinogenesis, 1994, vol. 10, p. 159.

    Article  CAS  Google Scholar 

  17. Woolf, T.F., Pool, W.F., Bjorge, S.M.,et al., Bioactivation and Irreversible Binding of the Cognition Activator Tarcine,Drug Metab. Dispos. Biol. Fate Chem., 1993, vol. 21, p. 874.

    PubMed  CAS  Google Scholar 

  18. Ding, X., Spink, D.C., Bhama, J.K.,et al., Metabolic Activation of 2,6-Dichlorobenzonitrile, an Olfactory Specific Toxicant,Mol. Pharmacol., 1996, vol. 49, p. 1113.

    PubMed  CAS  Google Scholar 

  19. Bond, J.A., Csanady, G.A., Leavens, T., and Medinsky, M.A., Research Strategy for Assessing Target Tissue Dosimetry of 1,3-Butadiene in Laboratory Animals and Humans.IARS Sci. Publ., 1993, vol. 127, p. 45.

    CAS  Google Scholar 

  20. Bogaards, J.J., Venekamp, J.C., and van Bladeren, P., The Biotransformation of Isoprene and the Two Isoprene Monoepoxides by Human Cytochrome P-450 Enzymes,Chem. Biol. Interact., 1996, vol. 102, p. 169.

    Article  PubMed  CAS  Google Scholar 

  21. Loeper, J., Descatoire, V., Letteron, P.,et al., Hepatotoxicity of Germander in Mice,Gastroenterol., 1994, vol. 106, p. 464.

    CAS  Google Scholar 

  22. Friedberg, T., Becher, R., Oesch, F., and Glatt, H.R., Studies on the Importance of Microsomal Epoxide Hydrolase in the Detoxification of Arene Oxides,Carcinogenesis, 1994, vol. 15, p. 171.

    Article  PubMed  CAS  Google Scholar 

  23. Oesch, F., Oesch-Bartlomowitz, B., Arens, J.,et al., Mechanism-based Predictions of Interactions,Environ. Health Perspect., 1994, vol. 102, suppl. 9, p. 5.

    PubMed  CAS  Google Scholar 

  24. Hassett, C., Aicher, L., Sidhu, J.S., and Omiecinski, C.J., Human Hepatic Microsomal Epoxide Hydrolase: Comparative Analysis of Polymorphic Expression,Arch. Biochem. Biophys., 1997, vol. 337, p. 275.

    Article  PubMed  CAS  Google Scholar 

  25. Lancaster, J.M., Brownlee, H.A., Bell, D.A.,et al., Microsomal Epoxide Hydrolase Polymorphism as a Risk Factor for Ovarian Cancer,Mol. Carcinogenesis, 1996, vol. 17, p. 160.

    Article  CAS  Google Scholar 

  26. Nakajima, T., Elovaara, E., Auttila, S.,et al., Expression and Polymorphism of Glutathione S-Transferases in Human Lungs,Carcinogenesis, 1995, vol. 16, p. 707.

    Article  PubMed  CAS  Google Scholar 

  27. Autilla, S., Luestrarinen, A., Hirvonen, A.,et al., Pulmonary Expression of GSTM3 in Lung Cancer Patients,Cancer Res., 1995, vol. 55, p. 3305.

    Google Scholar 

  28. Lin, H.J., Pnobst, N.M., Ingles, S.A.,et al., GST M1 Null Genotype, Smoking, and Prevalence of Colorectal Adenomas,Cancer Res., 1995, vol. 55, p. 1224.

    PubMed  CAS  Google Scholar 

  29. Mulder, T.P., Verspaget, H.W., Sier, C.F.,et al., GST π in Colorectal Tumors Is Predictive for Overall Survival,Cancer Res., 1995, vol. 55, p. 2696.

    PubMed  CAS  Google Scholar 

  30. Czarka, C.T., Preiffer, G.R., Hum, S.T.,et al., GST Activity and GST M-Expression in Subjects with Risk for Colorectal Cancer,Cancer Res., 1995, vol. 55, p. 2789.

    Google Scholar 

  31. Brockmoller, J., Cascorbi, I., Kerb, R., Roots, I., Combined Analysis of Inherited Polymorphisms in N-Acetyl-transferase 2, Glutathione S-Transferases M1 and T1, Microsomal Epoxide Hydrolase and Cytochrome P-450 Enzymes as Modulators of Bladder Cancer, Risk,Cancer Res., 1996, vol. 56, p. 3915.

    PubMed  CAS  Google Scholar 

  32. Farin, F.M., Bilger, L.G., Oda, D.,et al., Expression of Cytochrome P-450 and Microsomal Epoxide Hydrolase in Cervical and Oral Epithelial Cells Immortalized by Human Papilloma Virus,Carcinogenesis, 1995, vol. 16, p. 1391.

    Article  PubMed  CAS  Google Scholar 

  33. Bouchardy, C., Benhamon, S., and Dayer, P., The Effect of Tobacco on Lung Cancer Risk Depends on CYP2D6 Activity,Cancer Res., 1996, vol. 56, p. 251.

    PubMed  CAS  Google Scholar 

  34. Hirvonen, F., Pelin, K., Tammilehto, L.,et al., Inherited GST M1 and NAT2 Defects as Concurrent Risk Modifiers in Asbestos-related Human Malignant Mesothelioma,Cancer Res. 1995, vol. 55, p. 2981.

    PubMed  CAS  Google Scholar 

  35. Ambrosone, C.B., Freudenheim, J.L., Graham, S.,et al., Cytochrome P-450 A1 and Glutathione S-Transferase (M1) Genetic Polymorphism and Postmenopausal Breast Cancer Risk,Cancer Res., 1995, vol. 55, p. 3483.

    PubMed  CAS  Google Scholar 

  36. Newcomb, P.A., Storer, B.E., and Marcus, P.M., Cigarette Smoking in Relation to Risk of Large Bowel Cancer in Women,Cancer Res., 1995, vol. 55, p. 4906.

    PubMed  CAS  Google Scholar 

  37. Taioli, E., Grofts, F., Trachman, J.,et al., A Specific African—American CYPA1 Polymorphism Is Associated with Adenocarcinoma of the Lung,Cancer Res., 1995, vol. 55, p. 472.

    PubMed  CAS  Google Scholar 

  38. Law, M.R., Genetic Predisposition to Lung Cancer,Br. J. Cancer, 1990, vol. 61, p. 195.

    PubMed  CAS  Google Scholar 

  39. Nikachi, K., Imai, K., Hayashi, S.,et al. Genetic Susceptibility to Squamous Cell Carcinoma of the Lung in Relation to Cigarette Smoking Dose,Cancer Res., 1991, vol. 51, p. 5177.

    Google Scholar 

  40. Crofis, F. and Cosma, G., A Novel CYP1A1 Gene Polymorphism in African Americans,Carcinogenesis, 1993, vol. 9, p. 1729.

    Article  Google Scholar 

  41. Kelsey, K.T., Wienske, J.K., Spitz, M.R.,et al., Lung Carcinoma and CYP1A1 Gene Polymorphism,Carcinogenesis, 1994, vol. 15, p. 1121.

    Article  PubMed  CAS  Google Scholar 

  42. London, S.J., Daly, A.K., Fairbrother, K.S.,et al., Lung Cancer Risk in African Americans in Relation to a Race-Specific CYP1A1 Polymorphism,Cancer Res., 1995, vol. 55, p. 6035.

    PubMed  CAS  Google Scholar 

  43. Taioli, E., Trachman, J., Chen, X.,et al., A CYP1A1 Restriction Fragment Length Polymorphism Is Associated with Breast Cancer in African-American Women,Cancer Res., 1995, vol. 55, p. 3757.

    PubMed  CAS  Google Scholar 

  44. Guengerich, F.P., Johnson, W.E., Hong, Y.F.,et al., Involvement of Cytochrome P-450, Glutathione S-Transferase and Epoxide Hydrolase in the Metabolism of Aflatoxin B1 and Relevance to Risk of Human Liver Cancer,Environ. Health Perspect., 1996, vol. 104, suppl. 3, p. 352.

    Google Scholar 

  45. McGlynn, K.A., Rosvold, E.A., Lustbader, I.,et al., Susceptibility to Hepatocellular Carcinoma Is Associated with Genetic Variation in the Enzymatic Detoxification of Aflatoxin B1,Proc. Natl. Acad. Sci. USA, 1995, vol. 92, p. 2384.

    Article  PubMed  CAS  Google Scholar 

  46. Massey, T.E., Stewart, R.K., Daniels, J.M., and Liu, L., Biochemical and Molecular Aspects of Mammalian Susceptibility to Aflatoxin B1 Carcinogenicity,Proc. Soc. Exp. Biol. Med., 1995, vol. 208, p. 213.

    PubMed  CAS  Google Scholar 

  47. Kellermann, G., Luyten-Kellermann, V., and Shaw, C.R., Inducibility of Polycyclic Aromatic Hydrocarbon-Hydroxylase in Human Blood Lymphocytes,Am. J. Hum. Genet., 1973, vol. 25, p. 327.

    PubMed  CAS  Google Scholar 

  48. Nebert, D.W. and Atlas, S.A., Role of Genetics and Drug Metabolism in Human Cancer Risk inGenetics of Human Cancer, Mulvinill J.et al., Eds., New York: Raven, 1977, p. 301.

    Google Scholar 

  49. Pelkonen, O., Karki, N.T., and Sotaniemi, E.A.,Human Cancer. Its Characterization and Treatment, Davis, W.,et al., Eds., Amsterdam: Experta Med., 1980, p. 48.

    Google Scholar 

  50. Pelkonen, O., Vahakangai, K., Karki, N.T., and Sotaniemi, E.A., Inducibility of Benz[a]pyrene Hydroxylase Activity as a Lung Cancer Predictive Factor,Toxicol. Pathol., 1984, vol. 12, p. 256.

    Article  PubMed  CAS  Google Scholar 

  51. Pelkonen, O., Karki, N.T., Pokela, R., and Nuntinen, L., Seasonal Variation of Benz[a]pyrene Hydroxylase Activity in Human Blood Lymphocytes,Int. J. Cancer., 1987, vol. 39, p. 565.

    Article  PubMed  Google Scholar 

  52. Gelboin, H.V., Carcinogenesis, Drugs, and Cytochrome P-450,New Engl. J. Med., 1983, vol. 309, p. 105.

    Article  PubMed  CAS  Google Scholar 

  53. Shu-Xin Qu and Stacey, N.H., Formation and Persistence of DNA Adducts in Different Target Tissues of Rats after Multiple Administration of B[a]PCarcinogenesis, 1996, vol. 17, p. 53.

    Article  PubMed  CAS  Google Scholar 

  54. Wienke, J.K., Kelsey, K.T., Varkonyi, A.,et al., Correlation of DNA Adducts in Blood Mononuclear Cells with Tobacco Carcinogen-induced Damage in Human Lung,Cancer Res., 1995, vol. 55, p. 4910.

    Google Scholar 

  55. Moller, L., Grzybowska, C., Zeisig, M.,et al., Seasonal Variation of DNA Adduct Pattern in Human Lymphocytes Analyzed by32p-HPLC,Carcinogenesis, 1996, vol. 17, p. 61.

    Article  PubMed  CAS  Google Scholar 

  56. Kearns, G.L., Pharmacogenetics and Development: Are Infants and Children at Increased Risk for Adverse Outcomes,Curr. Opin. Pediatr., 1995, vol. 7, p. 220.

    Article  PubMed  CAS  Google Scholar 

  57. Kitteringham, N.R., Davis, C., Howard, N.,et al., Interindivudual and Interspecies Variation in Hepatic Microsomal Epoxide Hydrolase Activity,J. Pharmacol. Exp. Ther., 1996, vol. 278, p. 1018.

    PubMed  CAS  Google Scholar 

  58. Lillibridge, J.H., Amore, B.M., Slattery, J.T.,et al., Protein-Reactive Metabolites of Carbamazepine in Mouse Liver Microsomes,Drug Metab. Dispos., 1996, vol. 24, p. 509.

    PubMed  CAS  Google Scholar 

  59. Idle, J.R., Mangoub, A., Mbanefo, C.,et al., Polymorphic Hydroxylation of Debrisoquine in Nigerians,Br. J. Clin. Pharmacol., 1980, vol. 9, p. 112.

    Google Scholar 

  60. Vienneau, D.S., De Boni, U., and Wells, P.G., Potential Genoprotective Role of UDP-Glucuronosyltransferases in Chemical Carcinogenesis,Cancer Res., 1995, vol. 55, p. 1045.

    PubMed  CAS  Google Scholar 

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  1. Semenov Institute of Chemical Physics, Russian Academy of Sciences, ul. Kosygina 4, 117977, Moscow, Russia

    L. A. Piruzyan, V. A. Sukhanov & A. N. Saprin

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  1. L. A. Piruzyan
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Piruzyan, L.A., Sukhanov, V.A. & Saprin, A.N. Prognostic risk factor of the development of pathological processes based on polymorphism of xenobiotic metabolism enzymes. Hum Physiol 26, 224–231 (2000). https://doi.org/10.1007/BF02760097

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