DNA damage response upon environmental contaminants: An exhausting work for genomic integrity

Boutet-Robinet, Élisa; Bortoli, Sylvie; Huc, Laurence

doi:10.1016/j.cotox.2017.12.002

Cited by 2 publications

(1 citation statement)

References 28 publications

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“…HNE, at 0.5 µM and 2 h exposure, barely induced 53BP1 foci in CT cells, whereas it was described to be genotoxic in cerebral endothelial cells for doses higher than 1 µM after 3 h of exposure [49]. A previous study proposed that low DNA damage induced by an acute exposure to a low concentration of environmental toxicant can lead to an efficient DNA damage response, i.e., an efficient DNA repair and maintenance of cellular integrity [50]. In contrast, long-term exposure to HNE seems to trigger γH2AX foci in all cell lines, suggesting that the maintenance of DNA integrity could not be longer assured and could contribute to mutagenesis, in particular G:C > T:A mutations in proto-oncogenes like K-RAS [51].…”

Section: Discussionmentioning

confidence: 96%

Short-Term and Long-Term Carcinogenic Effects of Food Contaminants (4-Hydroxynonenal and Pesticides) on Colorectal Human Cells: Involvement of Genotoxic and Non-Genomic Mechanisms

Arnaud

Gauthier

Naour

et al. 2021

Cancers

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To investigate environmental impacts upon colorectal carcinogenesis (CRC) by diet, we assessed two western diet food contaminants: 4-hydroxynonenal (HNE), a major lipid peroxidation product neoformed during digestion, and a mixture of pesticides. We used human colonic cell lines ectopically eliciting varied genetic susceptibilities to CRC: the non-transformed human epithelial colonic cells (HCECs) and their five isogenic cell lines with the loss of APC (Adenomatous polyposis coli) and TP53 (Tumor protein 53) and/or ectopic expression of mutated KRAS (Kristen-ras). These cell lines have been exposed for either for a short time (2 -24 h) or for a long period (3 weeks) to 1 µM HNE and/or 10 µM pesticides. After acute exposure, we did not observe any cytotoxicity or major DNA damage. However, long-term exposure to pesticides alone and in mixture with HNE induced clonogenic transformation in normal HCECs, as well as in cells representing later stages of carcinogenesis. It was associated with genotoxic and non-genomic mechanisms (cell growth, metabolic reprogramming, cell mobility and epithelial-mesenchymal transition) depending on genetic susceptibility. This study demonstrated a potential initiating and promoting effect of food contaminants on CRC after long-term exposure. It supports that these contaminants can accelerate carcinogenesis when mutations in oncogenes or tumor suppressor genes occur.

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Section: Discussionmentioning

confidence: 96%