| First Author | Chu FF | Year | 2004 |
| Journal | Cancer Res | Volume | 64 |
| Issue | 3 | Pages | 962-8 |
| PubMed ID | 14871826 | Mgi Jnum | J:88070 |
| Mgi Id | MGI:3029090 | Doi | 10.1158/0008-5472.can-03-2272 |
| Citation | Chu FF, et al. (2004) Bacteria-Induced Intestinal Cancer in Mice with Disrupted Gpx1 and Gpx2 Genes. Cancer Res 64(3):962-968 |
| abstractText | Two glutathione peroxidase (GPX) isozymes, GPX-1 and GPX-2 (GPX-GI), are the major enzymes that reduce hydroperoxides in intestinal epithelium. We have previously demonstrated that targeted disruption of both the Gpx1 and Gpx2 genes (GPX-DKO) results in a high incidence of ileocolitis in mice raised under conventional conditions, which include the harboring of Helicobacter species [non-specific-pathogen-free (non-SPF) conditions]. In this study, we have characterized GPX-DKO mice that have microflora-associated intestinal cancers, which are correlated with increased intestinal pathology/inflammation. We found that GPX-DKO mice raised under germ-free conditions have virtually no pathology or tumors. After colonizing germ-free mice with commensal microflora without any known pathogens (SPF), <9% of GPX-DKO mice develop tumors in the ileum or the colon. However, about one-fourth of GPX-DKO mice raised under non-SPF conditions from birth or transferred from SPF conditions at weaning have predominantly ileal tumors. Nearly 30% of tumors are cancerous; most are invasive adenocarcinomas and a few signet-ring cell carcinomas. On the basis of these results, we conclude that GPX-DKO mice are highly susceptible to bacteria-associated inflammation and cancer. The sensitivity exhibited in these mice suggests that peroxidative stress plays an important role in ileal and colonic pathology and inflammation, which can lead to tumorigenesis. |
