Abstract

chemistry (IHC) with anti-5-methylcytosine. Serum folate and B12 were measured by radioimmunoassay and homocysteine was measured by HPLC. Tissue folate levels were assessed by a microbiological assay. RESULTS. There was a significant decrease in CpG methylation in the transgenic mice that correlated with an increasing degree of dysplasia. HF infection resulted in a non significant increase in global methyl content, whereas transgenic mice showed a significant and progressive decrease in methylation from IM to CIS (p<0.01). This gLOM was confirmed by IHC in both epithelial and stromal cells. Serum folate and B12 levels were not significantly different. Serum total homocysteine, however, was significantly elevated in transgenic mice (p<0.001) compared to WT with and without HF infection. Preliminary results suggest that there may be a decreasing trend in tissue folate content between transgenic HF infected and uninfected mice, but not between non-transgenic mice. CONCLUSIONS. These results suggest that neoplastic progression, but not HF-induced inflammatory changes alone, is associated with an early progressive global loss of methylation. These changes correlate with decreasing serum methyl donor levels (increasing tHCY levels) and in preliminary results with tissue methyl donor levels (tissue folate content). The findings indicate that gLOM is an early change in this model of gastric cancer that is specific to neoplasia and does not occur simply as a result of inflammation.

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