Development of carcinoid tumors of the glandular stomach and effects of eradication in Helicobacter pylori-infected Mongolian gerbils.

The relation between Helicobacter pylori (Hp) eradication and prevention of stomach carcinoid development has hitherto remained unclear. We therefore examined this problem using an Hp-infected and Hp-eradicated Mongolian gerbil (MG) model. Enterochromaffin-like (ECL) lesions (hyperplasia/dysplasia and carcinoid) were histopathologically evaluated in the glandular stomachs of Hp-infected and Hp-eradicated MGs. In addition, serum gastrin levels were analyzed. Hp infection induced significant increase in the development of ECL lesions in the glandular stomach, as well as serum gastrin levels as compared with non-infected MGs, while Hp eradication was associated with significant alleviation. The development of ECL lesions in the glandular stomach strongly correlated with titers of anti-Hp antibodies and serum gastrin levels in MGs. In conclusion, Hp infection induces carcinoid development, and Hp eradication prevents its occurrence in the glandular MG stomach, this being strongly linked with reduction in serum gastrin levels.

Lack of initiation activity of 4-oxo-2-hexenal, a peroxidation product generated from omega-3 polyunsaturated fatty acids, in an in vivo five-week liver assay.

Peroxidation products formed from polyunsaturated lipids have DNA damaging potential. 4-oxo-2-hexenal (4-OHE), generated by the oxidation of omega-3 fatty acids, has been demonstrated to be mutagenic in vitro as assessed in the Ames test. To examine the carcinogenic risk of 4-OHE in vivo, initiation activity was investigated in a five-week liver assay, established to be effective for screening of carcinogenic potential of mutagens. Seven-week-old male F344 rats underwent two-thirds partial hepatectomy (PH) and were administered 4-OHE intragastrically at doses of 128, 80, 64, 40, 32, 20, or 0 mg/kg body weight (b.w.) at 18 hours thereafter, then being fed on diet containing 0.015% 2-acetylaminofluorene from weeks 2 to 4. All rats were given with 0.8 ml/kg b.w. CCl4 at week 3. At week 5, all survivors were sacrificed and initiation activity was assessed with reference to induction of glutathione S-transferase placental form (GST-P) positive foci in the liver. Mortality was significantly increased to 72.7% in the 128 mg/kg b.w. dose group compared with 0.9% in the control group. However, the average number of GST-P positive foci in the "128" dose group was 3.26-/+1.66 foci/cm2, not significantly different from the control value (2.78?1.33). Areas of GST-P positive foci were also similar (1.11-/+0.5 and 1.53-/+1.33 mm2/cm2 in "128" and the control groups, respectively). These results showed 4-OHE to have no significant initiation activity in.

Intestinal phenotypes of stomach cancers arising after Helicobacter pylori eradication in carcinogen-treated Mongolian gerbils.

AIMS: We have previously demonstrated the importance of gastric and intestinal phenotypic expression for the histogenesis of stomach cancer. However, the phenotypes of stomach cancers arising after Helicobacter pylori (Hp) eradication have hitherto remained unclear. We therefore examined a series of lesions occurring after Hp eradication in the Mongolian gerbil (MG) model. METHODS: Totals of 6 and 20 advanced glandular stomach cancers were evaluated in Hp-eradicated and Hp-infected MGs treated with N-methyl-N-nitrosourea (MNU-MGs), using several gastrointestinal epithelial phenotypic markers. The lesions were divided phenotypically into gastric (G type), gastric-and-intestinal mixed (GI type), intestinal (I type), and null (N type) phenotypes. RESULTS: All 4 differentiated type lesions in Hp-eradicated MNU-MGs were classified as G type, while both of the undifferentiated lesions exhibit the GI type. In Hp-infected MNU-MGs, the lesions were classified as 10 G, 8 GI, and 2 I types, with undifferentiated type lesions having more intestinal phenotypic expression than their differentiated counterparts (P< 0.01). CONCLUSIONS: Our data suggest that the differentiated stomach cancers exhibit the G type in Hp-eradicated MNU-MGs, suggesting that a kind of non-neoplastic G type gland may be precancerous. Intestinalization may still occur, especially in undifferentiated stomach cancers, even if Hp eradication is successful.