Chapter 36 Nutrition and Colon Cancer FIGURE 36.1: (A) Aberrant crypt foci (ACF) and (B) mucin-depleted foci (MDF) in rat colon. ACF are visualized by staining whole mounts of colon with methylene blue. MDF are ACF that show no mucin staining using high-iron diamine alcian blue. Normal crypts stain black. Copyright 2016 Elsevier Inc. All rights
reserved. FIGURE 36.2: An overview of the pathway of chemical carcinogenesis. Indirect carcinogens can be detoxified through phase I and phase II metabolism, although for a few compounds, phase II metabolism can lead to carcinogen activation (dottedline). However, some indirect carcinogens are activated by phase I metabolism, leading to mutations in DNA through formation of DNA adducts. DNA repair mechanisms can remove the adducts. If mutation is extensive, this can result in cell death through apoptosis. However, if the DNA is not repaired correctly, and DNA replication occurs, this can lead to a permanent mutation,forming an initiated cell. Additional mutations or promoters of cell proliferation can lead to
hyperproliferation and potentially a tumor. Adapted from G.A. Belitsky, M.G. Yakubovskaya, Genetic polymorphism and variability of chemical carcinogenesis, Biokhimiya 73 (2008) 675689, http://www.protein.bio.msu.ru/biokhimiya/contents/v73/ full/73050675.html. Copyright 2016 Elsevier Inc. All rights reserved. FIGURE 36.3 An overview of phase I and phase II metabolism.Carcinogens can undergo oxidation reactions that allow
conjugation with glutathione by GSTs Alternatively, carcinogens can undergo hydrolysis or reduction reactions, and subsequently be sulfated by SULTs, acetylated by N-acetyltransferases, or glucuronidated by UGTs. The result is a more hydrophilic compound that can be excreted in the bile or urine. Adapted from https ://commons.wikimedia.org/wiki/File Xenobiotic_metabolism.png Copyright 2016 Elsevier Inc. All rights reserved.
FIGURE 36.4: Structure of two foodborne HAAs, 2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine (PhIP) and 2-amino3,4-dimethylimidazo[4,5-f] quinolone (MeIQ) and their DNA adducts N-(deoxyguanosin-8-yl)PhIP (dG-C8PhIP) and N(deoxyguanosin-8-yl)MeIQ (dG-C8MeIQ). Copyright 2016 Elsevier Inc. All rights reserved.
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