Data from <i>Enterococcus faecalis</i> Induces Aneuploidy and Tetraploidy in Colonic Epithelial Cells through a Bystander Effect

Abstract

<div>Abstract<p>Intestinal commensals are potential important contributors to the etiology of sporadic colorectal cancer, but mechanisms by which bacteria can initiate tumors remain uncertain. Herein, we describe mechanisms that link <i>Enterococcus faecalis</i>, a bacterium known to produce extracellular superoxide, to the acute induction of chromosomal instability. Immortalized human and nontransformed murine colonic epithelial cells, along with a mouse colonic ligation model, were used to assess the effect of <i>E. faecalis</i> on genomic DNA stability and damage. We found that this human intestinal commensal generated aneuploidy, tetraploidy, and γH2AX foci in HCT116, RKO, and YAMC cells. In addition, direct exposure of <i>E. faecalis</i> to these cells induced a G<sub>2</sub> cell cycle arrest. Similar observations were noted by exposing cells to <i>E. faecalis</i>–infected macrophages in a dual-chamber coculture system for detecting bystander effects. Manganese superoxide dismutase, catalase, and tocopherols attenuated, and caffeine and inhibitors of glutathione synthase exacerbated, the aneugenic effects and linked the redox-active phenotype of this intestinal commensal to potentially transforming events. These findings provide novel insights into mechanisms by which <i>E. faecalis</i> and intestinal commensals can contribute to cellular transformation and tumorigenesis. [Cancer Res 2008;68(23):9909–17]</p></div>