A critical discussion on diet, genomic mutations and repair mechanisms in colon carcinogenesis

• Published in: Toxicology letters 2017-01, Vol.265, p.106-116
• Main Authors: Sakita, Juliana Yumi, Gasparotto, Bianca, Garcia, Sergio Britto, Uyemura, Sergio Akira, Kannen, Vinicius
• Format: Article
• Language: English
• Subjects: Bowels; Cell Cycle - drug effects; Cell Cycle - genetics; Colon - drug effects; Colon - pathology; Colonic Neoplasms - etiology; Colonic Neoplasms - genetics; Colonic Neoplasms - pathology; Diet, Western - adverse effects; DNA Damage; DNA Repair; Environment; Environmental Pollutants - analysis; Environmental Pollutants - toxicity; Food Contamination - analysis; Genomic Instability - drug effects; Humans; Pollutants; Proliferation; Xenobiotics
• ISSN: 0378-4274; 1879-3169
• DOI: 10.1016/j.toxlet.2016.11.020

[Display omitted] •Western diet has an uncountable number of chemicals that affect humans.•Combining low concentrations of various chemicals leads to more powerful effects than an isolated exposure.•Low and late-cell cycle expressed genes are prone to undergo mutation.•Detection and repair mechanisms have a specific threshold to be activated throughout the G2/M phase.•Reactivation of these mechanisms during the M phase promotes genomic instability. 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.