胃黏膜癌变过程中端粒长度变化及其与细胞内DNA含量的关系

目的　分析不同病变胃黏膜细胞内端粒长度的差异，以及细胞内DNA含量，探讨端粒行为异常、细胞内DNA含量与胃黏膜癌变的关系。方法　应用Southern杂交分析细胞内端粒长度，应用流式细胞术测定细胞内DNA含量。结果　在172例胃镜活检标本中，正常胃黏膜，慢性浅表性胃炎(CSG)，伴0、1、2度肠化的慢性萎缩性胃炎(CAG)和胃癌组织的端粒长度，分别是(10.42±0.2)kb，(9.86±0.4)kb，(9.78±1.2)kb、(8.64±1.0)kb、(6.22±1.2)kb和(5.86±2.6)kb。45例胃癌手术标本结果　相似。流式细胞术分析细胞内DNA含量，在胃镜活检标本中，正常胃黏膜，CSG，伴0、1、2度肠化的CAG和胃癌组织的异倍体DNA检出率分别为0、0、0、10.00％、12.50％6和33.33％6。45例胃癌手术切除标本结果　相似。异倍体细胞内端粒长度明显短于二倍体细胞，异倍体细胞中端粒长度与DNA指数呈负相关(r=-0.91，P＜0.01)，即端粒越短，DNA指数越高。结论　端粒长度从正常胃黏膜、不同程度肠化胃黏膜到癌变胃黏膜逐渐缩短。在正常胃黏膜和CSG中未检出异倍体DNA，从1度、2度肠化到癌变胃黏膜异倍体DNA检出率逐渐增高，而在异倍体细胞中端粒长度和DNA指数呈负相关。推测，可能存在端粒愈短，DNA扩增愈活跃。端粒缩短伴DNA指数增加可能是胃癌发生的先兆。

Telomere, cellular DNA content and gastric mucosal carcinogenesis

Objective To investigate telomere length and cellular DNA content in different gastric lesion mucosa, and their relation with gastric mucosal carcinogenesis. Methods Telomere length were determined by southern hybridization. Cellular DNA content was detected by flow cytometry. Results Telomere length in intestinal metaplasia (IM) grade 2 was significantly shorter than that in normal gastric, IM grade 0 or grade 1. Telemere length of gastric carcinoma cells was the shortest in all of the biopsy specimens. Telomere length ratio in patients of corresponding surrounding nontumorous tissues with IM grade 2 was the largest in 45 resected gastric carcinoma. In flow cytometry, The aneuploid of gastric carcinoma (n= 18), chronic atrophic gastritis (CAG) contained IM grade 2 (n＝ 8), grade 1 (n= 40), grade 0 (n＝ 20), chronic superficial gastritis (CSG n＝46) and normal gastric mucosa (n = 10) was 33.3%, 12.5%, 10.0%, 0.0% ,0.0% and 0.0%, rspectively, in all of the biopsy specimens. In 45 resected gastric carcinoma specimens, Telomere length of 18 aneuploid was significantly shorter than that of 27 diploid. Furthermore reverse correlation was observed between telomere length and the DNA index in 18 aneuploid. Conclusions Telomere length were shortened as normal mucosa changed into intestinal metaplasia and more into gastric cancer. The normal and CSG mucosa shows no aneuploid. The positivity of DNA aneuploid tends to increase with the progression of intestinal metaplasia. In addition, telomere length and the DNA index show a reverse correlation. It is speculated that the shorter the telomere length the more amplificative activity the DNA. Telomere length and increased DNA index may be a predictor of stomach carcinogenesis.