不同病变胃粘膜的端粒长度与细胞内DNA含量

Telomere,cellular DNA content and gastric mucosal carcinogenesis

目的分析不同病变胃粘膜细胞内端粒长度的差异,以及细胞内 DNA 的含量,并探讨端粒行为异常、细胞内 DNA 含量与胃粘膜癌变的关系.方法对172例内镜活检和45例胃癌手术标本,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例内镜活检标本中,正常胃粘膜,慢性浅表性胃炎,伴0.1,2度肠化的慢性萎缩性胃炎和胃癌组织的端粒长度分别是10.4Kb±0.2Kb,9.9Kb±0.4Kb.9.8Kb±1.2Kb,8.6Kb±1.0Kb,6.2Kb±1.2Kb,5.9Kb±2.6Kb.在45例胃癌手术标本中结果相似.流式细胞术分析细胞内 DNA 含量的结果是,在门诊内镜活检标本中,正常胃粘膜,慢性浅表性胃炎,伴0,1,2度肠化的慢性萎缩性胃炎和胃癌组织的异倍体 DNA检出率分别为0.00%,0.00%,0.00%,10.00%,12.50%,33.33%在45例胃癌手术切除标本中结果也相似.而且异倍体细胞内的端粒长度明显短于二倍体细胞内的端粒长度,同时异倍体细胞中的端粒长度与 DNA 指数呈负相关(r=0.91,P<0.01),也就是端粒越短 DNA 指数越高.结论端粒长度从正常胃粘膜、不同程度肠化胃粘膜到癌变胃粘膜而逐渐缩短.在正常胃粘膜和慢性浅表性胃炎中未检出异倍体 DNA,从1度肠化、2度肠化到癌变的胃粘膜异倍体DNA 检出率逐渐增高,而且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 扩增愈活跃的情况,端粒缩短伴有 DNA 指数增加可能是胃癌发生的预兆.

AIM To investigate telomere length and cellular DNA content in different gastric mucosa,and the relationship among the telomere.cellular DNA content and gastric mucosal carcinogenesis. METHODS In 45 resected gastric carcinoma and 172 of the biopsy specimens,telomere length was determined by Southern hybridization,cellular DNA content was detected by flow cytometry.Telomere length of gastric carcinoma divided by that of corresponding surrounding stomach was telomere length ratio. RESULTS Telomere length in grade 2 intestinal metaplasia(IM)was significantly shorter than that in normal gastric mucosa,IM grade 0 or 1.Telemere length of gastric carcinoma was the shortest in all the biopsy specimens.Telomere length ratio in patients of corresponding surrounding nontumorous tissues with IM grade 2 was the largest in 45 resected gastric carcinomas. By flow cytometry,the aneuploids of gastric carcinoma (n=18),chronic atrophic gastritis(CAG)with IM grade 2 (n=8),1(n=40),0(n=20),chronic superficial gastritis (CSG,n=46)and normal gastric mucosa(n=10)were 33.3%,12.5%,10.0%,0.0%,0.0% and 0.0%, respectively.In 45 resected gastric carcinoma specimens, telomere length of 18 aneuploid was significantly shorter than that of 27 diploid.Reverse correlation was observed between telomere length and the DNA index in 18 aneuploid. CONCLUSION Telomere length is 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. Telomere length and the DNA index show a reverse correlation.It is tempting to speculate 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.