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A Protocol for Functional Assessment of Whole-Protein Saturation Mutagenesis Libraries Utilizing High-Throughput Sequencing
Published on: July 3, 2016
Nutrition and mutagenesis
Lynnette R Ferguson1, Martin Philpott
1Discipline of Nutrition, Faculty of Medical and Health Sciences, The University of Auckland, New Zealand. l.ferguson@auckland.ac.nz
Abstract:
Diet-related mutagenesis plays an etiologic role in chronic diseases, including cardiovascular disease and cancer. Many dietary mutagens are DNA reactive, leading to distinct spectra of base-pair substitution mutations and structural chromosome changes. Examples include aflatoxin B1, ochratoxin A, ptaquiloside, various pyrrolizidine alkaloids, heterocyclic amines including 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine, and polycyclic aromatic hydrocarbons such as benzo[a]pyrene. However, endogenously or exogenously formed reactive species, inhibitors of topoisomerase II enzymes (e.g., flavonoids), of DNA repair (e.g., caffeine), or of the mitotic spindle (possibly acrylamide), also cause mutations, including structural chromosome changes and copy number variants. Genomic instability also results from inadequate nutrient intake (e.g., folate and selenium). Antimutagens include vitamin C, carotenoids, chlorophyllin, dietary fibers, and plant polyphenols acting through various mechanisms. Polymorphisms in genes for nutrient uptake, metabolism, and excretion will affect dietary intake in determining individual risk of disease development. Human studies utilizing nutrigenomic/nutrigenetic technologies will be essential to quantifying and overcoming diet-related mutagenesis.
Insights
Diet-related mutagens can cause DNA damage, leading to chronic diseases like cancer. Understanding these mutagens and antimutagens is key to preventing diet-related diseases through nutrigenomics.
Area of Science:
- Toxicology
- Genetics
- Nutritional Science
Background:
- Diet-related mutagens contribute to chronic diseases, including cancer and cardiovascular disease.
- Many dietary mutagens are DNA-reactive, causing mutations and chromosomal changes.
- Genomic instability can also arise from nutrient deficiencies.
Purpose of the Study:
- To review the role of diet-related mutagens in disease etiology.
- To discuss mechanisms of mutagenesis and antimutagenesis.
- To highlight the importance of nutrigenomics in addressing diet-related risks.
Main Methods:
- Review of scientific literature on dietary mutagens and their effects.
- Identification of specific mutagenic compounds and their mechanisms of action.
- Discussion of antimutagenic compounds and their protective roles.
Main Results:
- Identified numerous dietary mutagens (e.g., aflatoxin B1, heterocyclic amines, polycyclic aromatic hydrocarbons) that induce DNA mutations.
- Highlighted endogenous reactive species and inhibitors of critical cellular processes as additional mutagenic factors.
- Noted that inadequate nutrient intake (e.g., folate, selenium) contributes to genomic instability.
- Listed various antimutagens (e.g., vitamin C, polyphenols) that counteract mutagenic effects through diverse mechanisms.
Conclusions:
- Diet-induced mutagenesis is a significant factor in chronic disease development.
- Genetic variations influence individual susceptibility to diet-related diseases.
- Nutrigenomic and nutrigenetic approaches are crucial for quantifying and mitigating diet-related mutagenesis.
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Cells are regularly exposed to mutagens—factors in the environment that can damage DNA and generate mutations. UV radiation is one of the most common mutagens and is estimated to introduce a significant number of changes in DNA. These include bends or kinks in the structure, which can block DNA replication or transcription. If these errors are not fixed, the damage can cause mutations, which in turn can result in cancer or disease depending on which sequences are...

