Bacteria-induced intestinal cancer in mice with disrupted Gpx1 and Gpx2 genes

Bacteria-induced intestinal cancer in mice with disrupted Gpx1 and Gpx2 genes
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DOI:
10.1158/0008-5472.can-03-2272
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发表时间:
2004-02-01
期刊:
影响因子:
11.2
通讯作者:
Doroshow, JH
Doroshow, JH
中科院分区:
医学1区
文献类型:
--
作者:
Chu, FF;Esworthy, RS;Doroshow, JH

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谷胱甘肽过氧化物酶(GPX)同工酶GPX-1和GPX-2(GPXG-1)是肠道上皮细胞中还原过氧化氢的主要酶。我们之前已经证明,靶向干扰GPX1和Gpx2基因(GPX-DKO)会导致在常规条件下饲养的小鼠回肠结肠炎的高发病率,其中包括幽门螺杆菌的存在[非特定病原体无(非SPF)条件]。在这项研究中,我们研究了患有微生物相关肠癌的GPX-DKO小鼠,这些癌症与肠道病理/炎症增加相关。我们发现,在无菌条件下饲养的GPX-DKO小鼠几乎没有病理或肿瘤。在无菌小鼠在没有任何已知病原体(唾液)的共生微生物区系中定居后,
Two glutathione peroxidase (GPX) isozymes, GPX-1 and GPX-2 (GPXG-1), 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 (SPIT),