TY - JOUR
T1 - Role of dietary xenobiotics-gene interactions in carcinogenesis
T2 - Protective effects of nutritional factors
AU - Romagnolo, Donato F.
AU - Degner, Stephanie C.
AU - Kemp, Michael Q.
AU - Hockings, Jennifer K.
AU - Selmin, Ornella
PY - 2006/8
Y1 - 2006/8
N2 - In this paper, we discuss how interactions between dietary xenobiotics and nutrients influence cancer risk by modulating overlapping biochemical pathways leading to repression of tumor suppressor genes, activation of tumor promoters, or both. Epidemiologic studies in humans suggested that diet is an important vehicle of exposure to various xenobiotics, including polycyclic aromatic hydrocarbons (PAHs), dioxins, and chlorinated hydrocarbons (CHs). The activation of the aromatic hydrocarbon receptor (AhR) pathway by PAHs and dioxins stimulates the expression of several genes including cytochrome P450s, which metabolize PAHs to highly mutagenic compounds that cause fixation of mutations in the p53 gene and repress the expression of the tumor suppressor gene, BRCA-1. Conversely, PAHs and dioxins have been shown to activate the expression of cyclooxygenase-2 (COX-2), whose protein product participates in the production of reactive PAH-metabolites and synthesis of proinflammatory prostaglandins (PGs). The carcinogenicity of CHs has been attributed to their ability to activate the expression of oncogenes including c-myc, and fatty acid activation of the peroxisome proliferator-activated receptor-α (PPARα). Dietary components that may protect against the activation of the AhR pathway include flavonoids, which comprise a large family of dietary phenolic phytochemicals found in fruits and vegetables. Nutrients such as dietary fatty acids may differentially influence the risk of cancer by inducing (linoleic and arachidonic acid) or repressing (conjugated linoleic acid (CLA); n-3PUFA) the expression of COX-2. Finally, we present original findings produced in our laboratory documenting the protective effects of natural (genestein) and synthetic (α-naphthoflavone) flavonoids against PAH-induced changes in gene expression.
AB - In this paper, we discuss how interactions between dietary xenobiotics and nutrients influence cancer risk by modulating overlapping biochemical pathways leading to repression of tumor suppressor genes, activation of tumor promoters, or both. Epidemiologic studies in humans suggested that diet is an important vehicle of exposure to various xenobiotics, including polycyclic aromatic hydrocarbons (PAHs), dioxins, and chlorinated hydrocarbons (CHs). The activation of the aromatic hydrocarbon receptor (AhR) pathway by PAHs and dioxins stimulates the expression of several genes including cytochrome P450s, which metabolize PAHs to highly mutagenic compounds that cause fixation of mutations in the p53 gene and repress the expression of the tumor suppressor gene, BRCA-1. Conversely, PAHs and dioxins have been shown to activate the expression of cyclooxygenase-2 (COX-2), whose protein product participates in the production of reactive PAH-metabolites and synthesis of proinflammatory prostaglandins (PGs). The carcinogenicity of CHs has been attributed to their ability to activate the expression of oncogenes including c-myc, and fatty acid activation of the peroxisome proliferator-activated receptor-α (PPARα). Dietary components that may protect against the activation of the AhR pathway include flavonoids, which comprise a large family of dietary phenolic phytochemicals found in fruits and vegetables. Nutrients such as dietary fatty acids may differentially influence the risk of cancer by inducing (linoleic and arachidonic acid) or repressing (conjugated linoleic acid (CLA); n-3PUFA) the expression of COX-2. Finally, we present original findings produced in our laboratory documenting the protective effects of natural (genestein) and synthetic (α-naphthoflavone) flavonoids against PAH-induced changes in gene expression.
KW - BRCA-1
KW - COX-2
KW - Dietary carcinogens
KW - Fatty acids
KW - Polyphenols
KW - p53
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U2 - 10.2174/157340106778017878
DO - 10.2174/157340106778017878
M3 - Review article
AN - SCOPUS:33747206860
SN - 1573-4013
VL - 2
SP - 205
EP - 214
JO - Current Nutrition and Food Science
JF - Current Nutrition and Food Science
IS - 3
ER -