title: Dietary influences on mutagenesis--where is this field going?
abstract: Early studies on dietary mutagenesis were mostly observational, with large numbers of potential dietary mutagens being identified from every conceivable dietary source. These included known dietary carcinogens such as aflatoxin B1 and benzo[a]pyrene, and hitherto unrecognized dietary mutagens, such as the pyrolysis products formed during the heating of proteinaceous materials (heterocyclic amines). The 1993 evaluation of 2-amino-3-methyl-3H-imidazo(4,5-j)quinoline as a probable human carcinogen by the International Agency for Research on Cancer was a landmark, as this was done in the absence of specific human carcinogenicity data, and strongly influenced by mutagenicity test data. In the 21st century, the field has moved from the identification of more and more mutagens, to molecular epidemiologic approaches that not only show a mutagenic effect but also seek to link it to a dietary (or environmental) cause. Effects of diet in stimulating chronic inflammation may lead to reactive species and thereby mutation as a secondary consequence, while dietary deficiencies and nutrient imbalances may be strong sources of mutagenesis. Recognition of the roles of nutrients in cell signaling processes and control of microRNAs suggest major influences on gene expression, in the absence of permanent DNA changes. Genome-wide association studies have highlighted new pathways such as JAK/STAT signaling that profoundly influence genomic instability and responses to dietary mutagens. With improved methodologies for DNA sequencing and epigenetic changes, it is time to apply more sophisticated approaches to recognizing and proving the role of diet as a primary modulator of mutagenesis in humans.
authors.affiliation: Discipline of Nutrition, Faculty of Medical & Health Science, The University of Auckland, Auckland, New Zealand. l.ferguson@auckland.ac.nz
authors.forename: Lynnette R
authors.initials: LR
authors.lastname: Ferguson
mesh_terms: D004032:Diet; D006801:Humans; D007249:Inflammation; D017720:Molecular Epidemiology; D016296:Mutagenesis / Q000235:genetics; D009153:Mutagens / Q000737:chemistry / Q000633:toxicity
chemical_list: D009153:Mutagens