Abstract
Chemical carcinogens appear to be the first class of foreign compounds demonstrated to be converted in vivo to reactive metabolites which bind covalently with tissue macromolecules (1,2), and a large literature now exists on this subject and its relevance to carcinogenesis by these agents (3–5). Considering the great structural heterogeneity of chemical carcinogens (5–8) and of drugs in general, it is not surprising that at high dosage levels a few drugs are known to be similarly activated in vivo to reactive metabolites which can exert acute toxic reactions through covalent binding with tissue components, especially proteins (9,10). Thus, although most drugs and their metabolites probably interact only noncovalently and thus reversibly with cellular molecules in their pharmacological actions, closer inspection of the metabolism of various drugs will doubtless reveal various degrees of covalent interactions in vivo. Such interactions may pose carcinogenic, mutagenic, teratogenic, allergenic, necrogenic, and possibly other hazards that must be weighed against the benefits provided by each drug in this category.
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References
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Miller, J.A., Miller, E.C. (1977). The Concept of Reactive Electrophilic Metabolites in Chemical Carcinogenesis: Recent Results with Aromatic Amines, Safrole, and Aflatoxin B1 . In: Jollow, D.J., et al. Biological Reactive Intermediates. Springer, Boston, MA. https://doi.org/10.1007/978-1-4613-4124-6_2
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