Cellular turnover of normal gastrointestinal epithelium assessed by changes in telomeric

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Abstract
Objectives The reasons why different areas of gastrointestinal mucosa exhibit widely different rates of malignant change are still poorly understood. Malignancy rates rise markedly with age. We therefore hypothesised that rates of malignant change might correlate with rates of ageing as judged by stem cell turnover. Telomeric DNA is lost with each cell division and so acts as a measure of the number of cell divisions undergone by stem cells. We measured telomeric:total DNA signal ratios in normal gastric (Helicobacter pylori-positive and H. pylori-negative), duodenal and colonic mucosa to see whether ratios correlated with propensity to malignancy. Patients Subjects undergoing diagnostic upper (n = 93) or lower (n = 45) gastrointestinal endoscopy, whose mucosa appeared macroscopically normal, sampled over a wide age range. Methods DNA was extracted from paired blood and mucosal samples (colonic or gastric and duodenal). Telomere length was assessed by dot blot hybridisation with an oligonucleotide-containing telomeric sequence compared with the signal obtained from total genomic DNA. Helicobacter status was assessed by Campylobacter-like organism (CLO) test and serologically. Results Telomeric signal ratios were scattered, but correlated within individuals. The ratios tended to decrease with age but the rates of decrease did not correlate with rates of malignant change. Gastric tissue had the shortest ratios and duodenal ratios decreased fastest. Conclusions The telomeric signal ratios did not suggest any obvious basis for differential rates of disease especially malignancy. Infection with H. pylori was not associated with lower gastric telomere ratios.