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Enhancement of Chemical Activation via Radical-Dependent Mechanisms: An Emerging Concept in Chemical-Chemical Interactions

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Part of the book series: Basic Life Sciences ((BLSC,volume 49))

Abstract

The biological effects of exogenous chemicals including drugs, are initiated through physiochemical interactions between the chemical and specific tissue macromolecules, such as enzymes, structural and receptor proteins, and nucleic acids. In most cases, such interactions provide the molecular basis for both the pharmacologic and toxic effects of xenobiotics. One of the possible results of the interaction of a chemical with cellular enzymes is its metabolism to a bioreactive intermediate.1 The reaction of either this initial reactive metabolite or a secondary reactive product with critical target molecules can then bring about changes in cellular function. Reactions which result in the enhanced activation of a chemical can then result in an increased pharmacologic or toxicologic effect. Chemical-mediated induction of enzymes involved in the metabolism of xenobiotics is a well-established mechanism whereby a chemical can indirectly enhance the activation and hence the potential toxic actions of another chemical2.

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References

  1. M.R. Boyd, Biochemical-mechanisms in chemical-induced lung injury: Roles of metabolic activation. CRC Crit. Rev. Toxicol. 7:103 (1980).

    Article  CAS  Google Scholar 

  2. R.W. Estabrook and E. Lindenlaub, eds, “The Induction of Drug Metabolism,” F.K. SchattauerVerlag, Stuttgart-New York (1979).

    Google Scholar 

  3. E. Dybing, S.D. Nelson, J.R. Mitchell, H.A. Sasame, and J. R. Gillette, Oxidation of alpha-methydopa and other catechols by cytochrome P-450-generated superoxide anion: Possible mechanism of methyldopa hepatitis, Mol. Pharmacol. 12:911 (1976).

    PubMed  CAS  Google Scholar 

  4. S.D. Nelson, J.R. Mitchell, E. Dybing, and H.A. Sasame, Cytochrome P-450-mediated oxidation of 2-hydroxyestrogens to reactive intermediates, Biochem. Biophys. Res. Commun. 70:1157 (1976).

    Article  PubMed  CAS  Google Scholar 

  5. M.E. McManus and D.S. Davies, Paraquat stimulated binding of dopa to liver and lung microsomal protein, Xenobiotica 10:745 (1980).

    Article  PubMed  CAS  Google Scholar 

  6. G.A. Reed, E.A. Brooke, and T.A. Eling, Phenylbutazone-dependent epoxidation of 7,8-dihydroxy-7,8-dihydrobenzo(a)pyrene. J. Biol. Chem. 259:5591 (1984).

    PubMed  CAS  Google Scholar 

  7. M.T. Kuo and C.W. Hardie, Characterization of chain breakage in DNA by bleomycin, Biochim. Biophys. Acta 335:109 (1973).

    CAS  Google Scholar 

  8. M.A. Trush, E.G. Mimnaugh, E. Ginsburg, and T.E. Gram, Studies on the interaction of bleomycin A2 with rat lung microsomes I. Characterization of factors which influence bleomycin-mediated DNA chain breakage, J. Pharmacol. Exp. Ther. 221:152 (1982).

    PubMed  CAS  Google Scholar 

  9. R.M. Burger, J. Peisach and S.B. Horwitz, Activated bleomycin: a transient complex of drug, iron and oxygen that degrades DNA, J. Biol. Chem. 256:11634 (1984).

    Google Scholar 

  10. A.P. Grollman, M. Takeshita, K.M.R. Pillar, and F. Johnson, Origin and cytotoxic properties of base propenals from DNA, Cancer Res. 45:1127 (1985).

    PubMed  CAS  Google Scholar 

  11. M.A. Trush, E.G. Mimnaugh, E. Ginsburg, and T.E. Gram, Studies on the interaction of bleomycin A2 with rat lung microsomes. II. Involvement of adventitious iron and reactive oxygen in bleomycin-mediated DNA chain breakage, J. Pharmacol. Exp Ther. 221:159 (1982).

    PubMed  CAS  Google Scholar 

  12. M.A. Trush, K.A. Kennedy, B.K. Sinha, and E.G. Mimnaugh, Bleomycinmediated deoxyribrose cleavage in rabbit lung nuclei, The Pharmacologist 25:225 (1983).

    Google Scholar 

  13. N. Yamanaka, M. Fukushima, T. Koto, K. Koizumi, and K. Ota, Experimental results with the combination of bleomycin plus mitomycin C, in: “Recent Results in Cancer Research,” S.K. Carter, H. Umezawa, J. Douros and Y. Sakurai, eds., Springer-Verlag, Berlin, (1978).

    Google Scholar 

  14. H. Witschi and S. Lock, Toxicity of butylated hydroxytoluene in mouse following oral administration, Toxicology 9:137 (1978).

    Article  PubMed  CAS  Google Scholar 

  15. T. Mizutani, I. Ishida, K. Yamamoto, and K. Tajima, Pulmonary toxicity of butylated hydroxytoluene and related alkylphenols: Structural requirements for toxicity potency in mice, Toxicol. Appl. Pharmacol. 62:273 (1982).

    Article  PubMed  CAS  Google Scholar 

  16. D.C. Thompson, Y.N. Cha, and M.A. Trush, The peroxidative activation of butylated hydroxytoluene to BHT-quinone methhide and stilbenequinone, in “Biological Reactive Intermediates, III.,” J.J. Kocsis, D.J. Jollow, C.M. Witmer, J.O. Nelson and R. Snyder, eds., Plenum Press, New York, (1986).

    Google Scholar 

  17. D.C. Thompson and M.A. Trush, The toxicological implications of the interaction of butylated hydroxytoluene with other antioxidants and phenolic chemicals, Fd. Chem. Toxicol. 24:1189 (1986).

    Article  CAS  Google Scholar 

  18. T. Kurechi and T. Kato, Studies on the antioxidants. XVI. Synergistic reactions between butylated hydroxyanisole and butylated hydroxytoluene in hydrogen donation to 2,2-diphenyl-1-picrylhydrazyl, Chem. Pharm. Bull, Tokyo 30:2964 (1982).

    Article  CAS  Google Scholar 

  19. D.C. Thompson and M.A. Trush; Studies on the mechanism of BHT-induced mouse lung toxicity by BHA, The Pharmacologist 28:216 (1986).

    Google Scholar 

  20. V.M. Samokyszyn and L.J. Marnett, Hydroperoxide-dependent cooxidation of 13-cis-retinoic by prostaglandin H synthase, J. Biol. Chem. 262:14119 (1987).

    PubMed  CAS  Google Scholar 

  21. R.A. Lovstad, Activating effect of chlopromazine on the peroxidasecatalyzed oxidation of catecholamines, Gen. Pharmacol. 10:437 (1979).

    Article  PubMed  CAS  Google Scholar 

  22. V.V. Subrahmanyam and P.J. O’Brien, Phenol oxidation product(s) formed by a peroxidase reaction that bind to DNA, Xenobiotica 15:873 (1985).

    Article  PubMed  CAS  Google Scholar 

  23. D.A. Eastmond, M.T. Smith, and R.D. Irons, An interaction of benzene metabolites reproduces the myelotoxicity observed with benzene exposure, Toxicol. Appl. Pharmacol. 91:85 (1987)

    Article  PubMed  CAS  Google Scholar 

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© 1988 Plenum Press, New York

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Trush, M.A., Thompson, D.C. (1988). Enhancement of Chemical Activation via Radical-Dependent Mechanisms: An Emerging Concept in Chemical-Chemical Interactions. In: Simic, M.G., Taylor, K.A., Ward, J.F., von Sonntag, C. (eds) Oxygen Radicals in Biology and Medicine. Basic Life Sciences, vol 49. Springer, Boston, MA. https://doi.org/10.1007/978-1-4684-5568-7_118

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  • DOI: https://doi.org/10.1007/978-1-4684-5568-7_118

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4684-5570-0

  • Online ISBN: 978-1-4684-5568-7

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