DNA damage induced by chronic inflammation contributes to colon carcinogenesis in mice
J. Clin. Invest. Lisiane B. Meira, et al. 118:2516 doi:10.1172/JCI35073 [Go to this article.]

Figure 4
Increased severity of stomach pathology in Aag^–/– versus Aag^+/+ animals infected with H. pylori. (A) Histopathology of gastric disease and mucosal metaplasia induced by H. pylori infection in the stomach mucosa of Aag^+/+ or Aag^–/– mice. Uninfected Aag^+/+ mouse stomach showed normal microscopic architecture (H&E) and a thin surface lining of gastric-type neutral mucins (red; AB/PAS), and anti-TFF2 stained intermittent mucous neck cells within normal oxyntic mucosa. Uninfected Aag^–/– mice were indistinguishable from the uninfected Aag^+/+, so only the Aag^+/+ is shown. For infected Aag^–/– mice, moderate gastritis with marked mucous metaplasia, hyperplasia, and oxyntic atrophy (loss of parietal and chief cells) was observed (H&E). Hyperplastic mucous neck cell population replaced resident zymogenic cells, secreting a mixture of gastric (red) and intestinal-type (acidic, blue) mucins (AB/PAS). Mucous metaplasia associated with expanded mucous neck cell population highlighted by TFF2 immunoreactivity. For infected Aag^+/+ mice, gastritis but minimal oxyntic alterations were observed (H&E). Mucous neck cells were significantly reduced in number in the Aag^+/+ H. pylori–infected mouse (AB/PAS). Fewer TFF2-positive mucous neck cells were observed in the infected Aag^+/+ mouse. Scale bars: 160 μm. (B) Pathology scores for infected Aag^+/+ (circles) and infected Aag^–/– (diamonds) mice. (C) Serum IgG1 and IgG2c responses to H. pylori in Aag^–/– and Aag^+/+ mice 32 weeks after infection. (D) H. pylori colonization levels in the stomach. Data presented as mean ± SD of log-transformed CFU/μg of genomic DNA.