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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: OBJECTIVE, METHODS, RESULTS. Meshes: Aldehydes, Animals, Autocrine Communication, Biopsy, Bystander Effect, Coculture Techniques, Colon, Colorectal Neoplasms, DNA Damage, Disease Models, Animal, Enterococcus faecalis, Epithelial Cells, G2 Phase Cell Cycle Checkpoints, Glutathione Transferase, Gram-Positive Bacterial Infections, HCT116 Cells, Histones, Humans, Interleukin-10, Macrophages, Mice, Mice, Knockout, RNA Interference, Spindle Apparatus, Stathmin, Tetraploidy, Time Factors, Transfection.
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Does 4-hydroxy-2-nonenal mediate genotoxicity and bystander effects caused by Enterococcus faecalis-infected macrophages? Context: Enterococcus faecalis is a human intestinal commensal that produces extracellular superoxide and promotes chromosome instability via macrophage-induced bystander effects. We investigated the ability of 4-hydroxy-2-nonenal (4-HNE), a diffusible breakdown product of ω-6 polyunsaturated fatty acids, to mediate these effects. 4-HNE was purified from E faecalis-infected macrophages; its genotoxicity was assessed in human colon cancer (HCT116) and primary murine colon epithelial (YAMC) cell lines. 4-HNE induced G(2)-M cell cycle arrest, led to formation γH2AX foci, and disrupted the mitotic spindle in both cell lines. Binucleate tetraploid cells that formed after incubation with 4-HNE were associated with the activation of stathmin and microtubule catastrophe. Silencing glutathione S-transferase α4, a scavenger of 4-HNE, increased the susceptibility of epithelial cells to 4-HNE-induced genotoxicity. Interleukin-10 knockout mice colonized with superoxide-producing E faecalis developed inflammation and colorectal cancer, whereas colonization with a superoxide-deficient strain resulted in inflammation but not cancer. 4-HNE-protein adducts were found in the lamina propria and macrophages in areas of colorectal inflammation.
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4-HNE can act as an autochthonous mitotic spindle poison in normal colonic epithelial and colon cancer cells. This finding links the macrophage-induced bystander effects to colorectal carcinogenesis. Final Decision: yes