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- Goldman, Radoslav, Shields, Peter G.
- Journal of nutrition 2003 v.133 no.3 pp. 965S-973S
- DNA, DNA damage, DNA methylation, DNA repair, aflatoxins, antioxidants, biomarkers, blood, carcinogenesis, cell death, diet, foods, genes, genetic traits, heterocyclic amines, ingestion, mutagenesis, mutagenicity, neoplasms, polycyclic aromatic hydrocarbons, risk, urine
- Several lines of evidence indicate that diet and dietary behaviors can contribute to human cancer risk. One way that this occurs is through the ingestion of food mutagens. Sporadic cancers result from a gene-environment interactions where the environment includes endogenous and exogenous exposures. In this article, we define environment as dietary exposures in the context of gene-environment interactions. Food mutagens cause different types of DNA damage: nucleotide alterations and gross chromosomal aberrations. Most mutagens begin their action at the DNA level by forming carcinogen-DNA adducts, which result from the covalent binding of a carcinogen or part of a carcinogen to a nucleotide. However the effect of food mutagens in carcinogenesis can be modified by heritable traits, namely, low-penetrant genes that affect mutagen exposure of DNA through metabolic activation and detoxification or cellular responses to DNA damage through DNA repair mechanisms or cell death. There are some clearly identified (e.g., aflatoxin) and suspected (e.g., N-nitrosamines, polycyclic aromatic hydrocarbons or heterocyclic amines) food mutagens. The target organs for these agents are numerous, but there is target-organ specificity for each. Mutagenesis however is not the only pathway that links dietary exposures and cancers. There is growing evidence that epigenetic factors, including changes in the DNA methylation pattern, are causing cancer and can be modified by dietary components. Also DNA damage may be indirect by triggering oxidative DNA damage. When considering the human diet, it should be recognized that foods contain both mutagens and components that decrease cancer risk such as antioxidants. Thus nutritionally related cancers ultimately develop from an imbalance of carcinogenesis and anticarcinogenesis. The best way to assess nutritional risks is through biomarkers, but there is no single biomarker that has been sufficiently validated. Although panels of biomarkers would be the most appropriate, their use as a reflection of target-organ risk remains to be determined. Also even when new biomarkers are developed, their application in target organs is problematic because tissues are not readily available. For now most biomarkers are used in surrogate tissues (e.g., blood, urine, oral cavity cells) that presumably reflect biological effects in target organs. This article reviews the role of food mutagens in mutagenesis and carcinogenesis and how their effects are modified by heritable traits and discusses how to identify and evaluate the effects of food mutagens.