McGarrity T J, Via E A, Colony P C
Department of Medicine, Milton S. Hershey Medical Center, Pennsylvania State University, Hershey 17033.
J Natl Cancer Inst. 1987 Dec;79(6):1375-82.
Regional differences in goblet cell glycoproteins have been demonstrated qualitatively and, to a limited extent, quantitatively in the normal adult colon. In disease states, alterations in these glycoproteins, particularly the sialoglycoproteins (SGs), have been reported. The present study defined parallel qualitative and quantitative changes in SGs in three colon regions during 1,2-dimethylhydrazine [(DMH) CAS: 540-73-8]-induced carcinogenesis. SGs were assessed histochemically by use of high iron diamine-Alcian blue (pH 2.5) staining, and tissue sialic acid levels were measured by a modified Warren assay. Two groups of inbred SD rats (n = 28) were pair-fed nutritionally complete liquid diets with 36% of calories supplied as ethanol or isocaloric carbohydrates. The dietary alcohol was added to selectively enhance rectal tumors, a region of prevalent tumors in humans. Both groups received 4 weeks of liquid diet followed by 4 weeks of standard laboratory chow with weekly sc injections of DMH. This 8-week cycle was repeated four times (32 wk). Animals from each group were sacrificed at 8, 16, 24, and 32 weeks, and adjacent tissues from proximal and distal colon and rectum were prepared for histology and biochemical assay. The results showed a progressive increase in sialomucin staining in normal-appearing mucosa in distal colon and rectum in both groups but not in the proximal colon. In contrast, tissue sialic acid increased in all three regions as early as 8 weeks, and significant increases were consistently present by 32 weeks. A different pattern was observed in tissue from frank tumors. Compared with normal-appearing mucosa, both sialomucin staining and tissue sialic acid levels were reduced in tumor tissue by 32 weeks. These studies indicated that tissue sialic acid levels may provide a simple and reliable screening technique in the early diagnosis of premalignant change in all regions of the colon.
在正常成年结肠中，杯状细胞糖蛋白的区域差异已得到定性证明，并且在一定程度上也得到了定量证明。在疾病状态下，已报道这些糖蛋白，特别是唾液酸糖蛋白（SGs）会发生改变。本研究确定了在1,2 - 二甲基肼[（DMH）CAS：540 - 73 - 8]诱导的致癌过程中，三个结肠区域SGs的平行定性和定量变化。通过高铁二胺 - 阿尔辛蓝（pH 2.5）染色对SGs进行组织化学评估，并通过改良的沃伦分析法测量组织唾液酸水平。两组近交系SD大鼠（n = 28）成对喂养营养完全的液体饮食，其中36%的热量由乙醇或等热量碳水化合物提供。添加膳食酒精是为了选择性地增加直肠肿瘤，直肠是人类肿瘤高发区域。两组均接受4周的液体饮食，随后4周给予标准实验室饲料，并每周皮下注射DMH。这个8周的周期重复四次（32周）。每组动物在第8、16、24和32周处死，取自近端结肠、远端结肠和直肠的相邻组织用于组织学和生化分析。结果显示，两组远端结肠和直肠外观正常的黏膜中唾液黏蛋白染色均呈渐进性增加，但近端结肠未出现这种情况。相反，早在第8周时，所有三个区域的组织唾液酸就增加了，到32周时一直显著增加。在明显肿瘤的组织中观察到不同的模式。与外观正常的黏膜相比，到32周时肿瘤组织中的唾液黏蛋白染色和组织唾液酸水平均降低。这些研究表明，组织唾液酸水平可能为结肠所有区域癌前病变的早期诊断提供一种简单可靠的筛查技术。
