Analyses of clonality and genomic changes in the regeneration of gastric mucosa

1. 我们分析了冻疮、儿茶酚治疗和放射治疗中再生胃腺的克隆性。组织学和遗传学均显示再生腺体单克隆性和BALB/c优良菌株变异，但未发现性别差异2。我们的隐窝分离技术尚未成功分离再生腺体，因为它们与基质有很强的附着性，并且结构脆弱，在分离过程中容易被破坏。放射诱导的大鼠胃粘膜肠化生通常与再生腺体有关。为了检查遗传变化，分离腺体并使用胃和肠细胞分化标记在组织学上将其分为几个亚型。目前正在对p53、K-ras、H-ras和APC基因的变化进行分析。我们还关注了暴露于儿茶酚的mnu诱导嵌合小鼠腺胃再生与致癌步骤之间的关系。该模型粘膜中均可见再生上皮、增生性上皮、腺瘤和癌。在多克隆组织背景下，再生和增生性上皮在单位腺体水平上被证明是单克隆的。腺瘤和大多数癌为单克隆，但少数大的癌可能是分散的肿瘤融合而成的多克隆。在嵌合体中也保留了致癌性的菌株差异。BrdU给药后，正常胃腺粘膜的增殖无明显差异。然而，生长到粘膜下层的病变，经常在增生性上皮中观察到，表现出BALB/c优势，在这种情况下，提示细胞反应的品系差异。目前正在调查所观察到的病变之间的相互关系。

1. We analyzed clonality of regenerative gastric glands in cases of freeze-ulceration, catechol administration, and irradiation. Monoclonality of regenerating glands and a BALB/c-superior strain variation were demonstrated both histologically and genetically, but no sex difference was found.2.Isolation of regenerative glands by our crypt-isolation technique has not yet been successful because of strong attachment to the stroma and a fragile structure making them susceptible to destruction during isolation process. Radiation- induced intestinal metaplasia in the rat gastric glandular mucosa is frequently- associated with regenerative glands. In order to examine genetic changes, glands were isolated and histologically divided into several subtypes using gastric and intestinal cell differentiation markers. Analyses of changes in p53, K-ras, H-ras, and APC genes are now under way.3. We have also concentrated attention on the relationship between regeneration and carcinogenic steps in the MNU-initiated chimeric mouse glandular stomach exposed to catechol. Regenerative epithelia, hyperplastic epithelia, adenomas, and carcinomas are all observed in the mucosa in this model. Regenerative and hyperplastic epithelia were demonstrated to be monoclonal at the level of the unit gland in a polyclonal tissue background. Adenomas and the most of carcinomas were monoclonal, but a few large carcinomas proved to be polyclonal probably due to fusion of discrete tumors. Strain differences in carcinogenecity were also preserved in the chimera. With BrdU administration to mice, no proliferative differences were apparent in the normal glandular stomach mucosa. However, lesions growing into the submucosa, frequently observed in hyperplastic epithelium, exhibited a BALB/c-superiority, in this context suggesting strain differences in cellular responses. The interrelationships of the observed lesions are now under investigation.