Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2012 Jul 16;25(7):1316-83.
doi: 10.1021/tx300132k. Epub 2012 May 10.

Contributions of human enzymes in carcinogen metabolism

Slobodan Rendic  1 , F Peter Guengerich
Affiliations
Review

Contributions of human enzymes in carcinogen metabolism

Slobodan Rendic et al. Chem Res Toxicol. .

Abstract

Considerable support exists for the roles of metabolism in modulating the carcinogenic properties of chemicals. In particular, many of these compounds are pro-carcinogens that require activation to electrophilic forms to exert genotoxic effects. We systematically analyzed the existing literature on the metabolism of carcinogens by human enzymes, which has been developed largely in the past 25 years. The metabolism and especially bioactivation of carcinogens are dominated by cytochrome P450 enzymes (66% of bioactivations). Within this group, six P450s--1A1, 1A2, 1B1, 2A6, 2E1, and 3A4--accounted for 77% of the P450 activation reactions. The roles of these P450s can be compared with those estimated for drug metabolism and should be considered in issues involving enzyme induction, chemoprevention, molecular epidemiology, interindividual variations, and risk assessment.

PubMed Disclaimer

Figures

Figure 1
Figure 1
General paradigm of metabolism of chemical carcinogens.
Figure 2
Figure 2
Enzyme contributions to activation of carcinogens (from Table 1). A: Fractions of activation reactions attributed to groups of enzymes. The analysis is based on 713 reactions. B: Fractions of P450 activation reactions attributed to individual human P450 enzymes (from a total of 473 reactions considered). See text for discussion.
Figure 2
Figure 2
Enzyme contributions to activation of carcinogens (from Table 1). A: Fractions of activation reactions attributed to groups of enzymes. The analysis is based on 713 reactions. B: Fractions of P450 activation reactions attributed to individual human P450 enzymes (from a total of 473 reactions considered). See text for discussion.
Figure 3
Figure 3
Diol-epoxide pathway of benzo[a]pyrene activation.
Figure 4
Figure 4
Oxidation of AFB1 by P450 3A4.
Figure 5
Figure 5
Conjugation of ethylene dibromide with GSH.
Figure 6
Figure 6
Analysis of types of activation reactions (data of Table 1, total of 799 reactions). See text for discussion.
Figure 7
Figure 7
Analysis of detoxication reactions. A: Enzymes involved in detoxication. B: Reactions involved in detoxication. Data are from Table 4 (total of 281 reactions). See text for discussion.
Figure 7
Figure 7
Analysis of detoxication reactions. A: Enzymes involved in detoxication. B: Reactions involved in detoxication. Data are from Table 4 (total of 281 reactions). See text for discussion.
See this image and copyright information in PMC

References

    1. Hill J, Baldwin R. In: Cautions Against the Immoderate Use of Snuff. 2nd ed Jackson J, editor. London: 1761.
    1. Rehn L. Über Blasentumoren bei Fuchsinarbeitern. Archiv. Clin. Chirgurie. 1895;50:588–600.
    1. Yamagiwa K, Ichikawa K. Experimentelle Studie über die Pathogenese der Epithelialgeschwulste. Mitt. Med. Fak. Tokio. 1915;15:295–344.
    1. Cook JW, Hewett CL, Hieger I. The isolation of a cancer-producing hydrocarbon from coal tar. Parts I, II, and III. J. Chem. Soc. 1933:394–405.
    1. Fieser LF. Carcinogenic activity, structure and chemical reactivity of polynuclear hydrocarbons. Am. J. Cancer. 1938;34:37–124.

Publication types