title: A critical discussion on diet, genomic mutations and repair mechanisms in colon carcinogenesis.
abstract: Colon cancer is one of the most common malignancies and its etiology closely tied to dietary habits. Recent epidemiological data shows that colon cancer incidence is shifting to a much younger population. In this regard, some dietary components from a regular human meal might have various DNA-damaging compounds. Given that not every person endure cancer, the colonic malignancy develops throughout decades, and persistent DNA damage promotes cancer when induced at the proper intensity, a critical discussion of possible novel mechanisms by which carcinogens promote these tumors is urgently needed. Robust genomic sequencing analyses showed that low and late cell cycle expressed genes are prone to undergo mutation. Moreover, detection and repair mechanisms have a particular threshold to be activated throughout the G2/M phase, and reactivation of these devices during the M phase promotes genomic instability. Conditions of combined exposure to non-genotoxic concentrations of various carcinogens seem to act effectively through these weaknesses in genomic repair mechanisms. Therefore, we suggest that the natural tolerance of body defence mechanisms eventually become overwhelmed by the chronic exposure to different combinations and intensities of dietary mutagens leading to the high incidence of colon cancer in modern society.
authors.affiliation: Department of Toxicology, Bromatology, and Clinical Analysis, University of Sao Paulo, Ribeirao Preto, Brazil.
authors.forename: Juliana Yumi
authors.initials: JY
authors.lastname: Sakita
authors.affiliation: Department of Toxicology, Bromatology, and Clinical Analysis, University of Sao Paulo, Ribeirao Preto, Brazil.
authors.forename: Bianca
authors.initials: B
authors.lastname: Gasparotto
authors.affiliation: Department of Pathology, University of Sao Paulo, Ribeirao Preto, Brazil.
authors.forename: Sergio Britto
authors.initials: SB
authors.lastname: Garcia
authors.affiliation: Department of Toxicology, Bromatology, and Clinical Analysis, University of Sao Paulo, Ribeirao Preto, Brazil.
authors.forename: Sergio Akira
authors.initials: SA
authors.lastname: Uyemura
authors.affiliation: Department of Toxicology, Bromatology, and Clinical Analysis, University of Sao Paulo, Ribeirao Preto, Brazil. Electronic address: vinicius.kannen@fcfrp.usp.br.
authors.forename: Vinicius
authors.initials: V
authors.lastname: Kannen
mesh_terms: D002453:Cell Cycle / Q000187:drug effects / Q000235:genetics; D003106:Colon / Q000187:drug effects / Q000473:pathology; D003110:Colonic Neoplasms / Q000209:etiology* / Q000235:genetics / Q000473:pathology; D004249:DNA Damage; D004260:DNA Repair; D066273:Diet, Western / Q000009:adverse effects*; D004785:Environmental Pollutants / Q000032:analysis / Q000633:toxicity*; D005506:Food Contamination / Q000032:analysis; D042822:Genomic Instability / Q000187:drug effects; D006801:Humans
chemical_list: D004785:Environmental Pollutants
keywords: Bowels; Environment; Pollutants; Proliferation; Xenobiotics