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Metabolic Activation of Chemical Carcinogens

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Chemical Carcinogenesis

Part of the book series: Current Cancer Research ((CUCR))

Abstract

Many chemical carcinogens require metabolic activation to biologically reactive intermediates which if not detoxified will react with DNA (covalently) or will lesion DNA through the production of reactive oxygen species. The enzymes involved in bioactivation are often phase I enzymes (i.e., those involved in functionalization), while phase II enzymes are involved in conjugation of the functional groups leading to elimination of the carcinogen. Effective elimination can also depend on the presence/absence of transport systems. It is the balance of these events that often determines the carcinogenicity of a chemical in a target tissue and also explains why certain carcinogens give rise to tumors in different organs based on route of administration. In addition, the phase I and phase II enzymes are highly inducible and these genomic responses can determine whether bioactivation or detoxication predominates. Furthermore, many genes involved in these events are highly polymorphic leading to the concept of poor and rapid metabolizers of a particular carcinogen which in turn may govern individual susceptibility to carcinogen exposure.

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  1. Center of Excellence in Environmental Toxicology, Department of Pharmacology, University of Pennsylvania, Philadelphia, PA, USA

    Trevor M. Penning

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  1. School of Medicine, Dept. Pharmacology, University of Pennsylvania, Hamilton Walk 3260, Philadelphia, 19104, Pennsylvania, USA

    Trevor M. Penning

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Penning, T.M. (2011). Metabolic Activation of Chemical Carcinogens. In: Penning, T. (eds) Chemical Carcinogenesis. Current Cancer Research. Humana Press. https://doi.org/10.1007/978-1-61737-995-6_7

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  • DOI: https://doi.org/10.1007/978-1-61737-995-6_7

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