Abstract
The concept that chemically reactive metabolites of foreign substances could react covalently with cellular constituents to cause biological injury was introduced by J. A. Miller and E. C. Miller almost 40 years ago. 1–3 Since then considerable effort has been spent investigating the chemistry, biochemistry and biological consequences of reactive metabolic intermediates. Our laboratory has been interested in the metabolic activation, covalent binding and hepatotoxicity of two relatively simple organic compounds, bromobenzene and thiobenzamide. Our long term objective has been to determine the identity of their reactive metabolites, the chemistry of their covalent binding to cellular macromolecules and the relationship of the various types of covalent binding events to the biological changes which follow. This report summarizes some of our recent efforts toward these objectives.
Keywords
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
This is a preview of subscription content, log in via an institution.
Buying options
Tax calculation will be finalised at checkout
Purchases are for personal use only
Learn about institutional subscriptionsPreview
Unable to display preview. Download preview PDF.
References
E. C. Miller and J. A. Miller, The presence and significance of bound aminoazo dyes in the livers of rats fed p-dimethylaminoazobenzene. Cancer Res. 7: 468–480 (1947).
E. C. Miller and J. A. Miller, In vivo combinations between carcinogens and tissue constituents and their possible role in carcinogenesis. Cancer Res. 12: 547–556 (1952).
J. A. Miller, Carcinogenesis by chemicals: an overview. Cancer Res. 30: 559–576 (1970).
B. B. Brodie, W. D. Reid, A. K. Cho, G. Sipes, G. Krishna and J. R. Gillette, Possible mechanism of liver necrosis caused by aranatic organic compounds. Proc. Nat. Acad. Sci. (U.S.), 68: 160–164 (1971).
D. J. Jollow, J. R. Mitchell, N. Zampaglione and J. R. Gillette, Branobenzene-induced liver necrosis. Protective role of glutathione and evidence for 3,4-bromobenzene oxide as the hepatotoxic metabolite, Pharmacology. 11: 151–169 (1974).
S. Hesse, T. Wolf and M. Mezger, Involv orient of phenolic metabolites in the irreversible protein-binding of 14C-branobenzene catalyzed by rat liver microsomes. Arch. Toxicol., Suppl. 4, 358–362 (1980).
J. W. Dodgson, The reaction of p-benzoquinone with sulphurous acid and with alkali. Part I. J. Chem. Soc., 105: 2435–2443 (1914).
K. T. Finley, The addition-substitution chemistry of quinones, in: “The chemistry of quinoid compounds, S. Patai, ed., John Wiley and Sons, New York (1974), pp 880–900.
T. J. Monks, L. R. Pohl, J. R. Gillette, M. Hong, R. J. Highet, J. A. Ferrretti and J. A. Hinson, Stereoselective formation of two bromobenzene-glutathione conjugates. Chem.-Biol. Interactions 41: 203–216 (1982).
R. P. Hanzlik, K. Hogberg and C. M. Judson, Microsomal hydroxylation of specifically deuterated monosubstituted benzenes. Evidence for direct aromatic hydroxylation. Biochemistry 23: 3048–3055 (1984).
J. W. Daly, D. M. Jerina and B. Witkop, Arene oxides and the NIHshift: the metabolism, toxicity and carcinogenicity of aromatic compounds. Experientia 28: 1129–1149 (1972).
R. P. Hanzlik and J. R. Cashman, Micrrosomal metabolism of thioben-zamide and thiobenzamide S-oxide. Drug Metab. Disposition, 11: 201–205 (1983).
R. E. Tynes and E. Hodgson, Oxidation of thiobenzamide by the FAD-containing and cytochrome P-450-dependent monooxygenases of liver and lung microsomes. Biochen. Pharmacol. 33: 3419–3428 (1983).
M. Younes, Involvanent of reactive oxygen species in the microsomal S-oxidation of thiobenzamide. Experientia, 41: 479–480 (1985).
J. R. Cashman and R. P. Hanzlik, Oxidation and other reactions of thiobenzamide derivatives of relevance to their hepatotoxicity. J. Org. Chem. 47: 4645–4650 (1982).
R. P. Hanzlik, J. R. Cashman and G. J. Traiger, Relative hepatotoxicityof substituted thiobenzamides and thiobenzamide S-oxides in the rat. Toxicol. Appl. Pharmacol. 55: 260–272 (1980).
J. R. Cashman, K. K. Parikh, G. J. Traiger and R. P. Hanzlik, Relative hepatotoxicity of ortho and meta monosubstituted thiobenzamides in the rat. Chem.-Biol. Interactions 45: 341–347 (1983).
J. R. Cashman, G. J. Traiger and R. P. Hanzlik, Pneumotoxic effects of thiobenzamide derivatives. Toxicology, 23: 85–93 (1982).
R. P. Hanzlik, K. P. Vyas and G. J. Traiger, Substituent effects on the hepatotoxicity of thiobenzamide derivatives in the rat. Toxicol. Appl. Pharmacol., 46: 685–694 (1978).
J. R. Cashman, Ph.D. Thesis, University of Kansas, 1982.
D. W. Gottschall, D. A. Penney, G. J. Traiger and R. P. Hanzlik, Oxidation of N-methylthiobenzamide and N-methylthiobenzamide S-oxide by liver and lung microsomes. Toxicol. Appl. Pharmacol., 78: 332–341 (1985).
D. A. Penney, D. W. Gottschall, R. P. Hanzlik and G. J. Traiger, The role of metabolism in N-methylthiobenzamide-induced pneunotoxicity. Toxicol. Appl. Pharmacol. 78: 323–331 (1985).
M. H. Griffiths, J. A. Moss, J. A. Rose, and D. E. Hathway, The comparative metabolism of 2,6-dichlorothiobenzamide (Prefix) and 2,6-dichlorothiobenzonitrile in the dog and rat. Biochem. J. 98: 770–781 (1966).
R. P. Hanzlik, Effects of substituents of reactivity and toxicity of chemically reactive intermediates. Drug Metab. Rev. 13: 207–234 (1982).
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1986 Plenum Press, New York
About this chapter
Cite this chapter
Hanzlik, R.P. (1986). Chemistry of Covalent Binding: Studies with Bromobenzene and Thiobenzamide. In: Kocsis, J.J., Jollow, D.J., Witmer, C.M., Nelson, J.O., Snyder, R. (eds) Biological Reactive Intermediates III. Advances in Experimental Medicine and Biology, vol 197. Springer, Boston, MA. https://doi.org/10.1007/978-1-4684-5134-4_3
Download citation
DOI: https://doi.org/10.1007/978-1-4684-5134-4_3
Publisher Name: Springer, Boston, MA
Print ISBN: 978-1-4684-5136-8
Online ISBN: 978-1-4684-5134-4
eBook Packages: Springer Book Archive