Sugihara H, Tsuchihashi Y, Hattori T, Fukuda M, Fujita S
J Cancer Res Clin Oncol. 1985;110(2):87-94. doi: 10.1007/BF00402717.
Signet ring cell carcinoma was induced in canine stomachs by N-ethyl-N'-nitro-N-nitrosoguanidine, and modes of cell proliferation and turnover in the carcinoma were studied by 3H-thymidine autoradiography in conjunction with morphometric analysis. From 2 to 15 months after the cessation of 8 months carcinogen treatment, carcinomas in an early stage were obtained. Most of the cancer tissues confined to the lamina propria showed a layered structure. This comprised three layers; the superficial and the deep layer were composed of signet ring cells, and the middle layer was composed of small round cells. The dogs were labeled with 3H-thymidine by s.c. injection and by local infusion of the celiac artery. Flash-labeled autoradiographs revealed that most 3H-thymidine incorporating cancer cells were located around the middle layer, with a small amount of mucin. Using a pulse labeling experiment, those labeled carcinoma cells were shown to migrate from the middle layer towards the surface. Morphometric analysis of the autoradiographs showed that the small cells in the middle layer migrated upwards and produced mucin to become full-blown signet ring cells by 5.5 days. In 15 days, most labeled cancer cells in the superficial layer had disappeared. This mode of cellular turnover appeared to mimic a cell renewal system of the normal gastric mucosa. If the cancer cells turn over in this way, the tumor must grow slowly, remaining as an intramucosal cancer for a relatively long period.
用N-乙基-N'-硝基-N-亚硝基胍在犬胃中诱发印戒细胞癌，并通过3H-胸腺嘧啶核苷放射自显影结合形态计量分析研究癌组织中的细胞增殖和更新模式。在8个月致癌剂治疗停止后2至15个月，获得了早期癌组织。大多数局限于固有层的癌组织呈现分层结构。该结构由三层组成；表层和深层由印戒细胞组成，中间层由小圆形细胞组成。通过皮下注射和腹腔动脉局部灌注给犬注射3H-胸腺嘧啶核苷。快速标记放射自显影片显示，大多数掺入3H-胸腺嘧啶核苷的癌细胞位于中间层周围，含有少量粘蛋白。通过脉冲标记实验表明，那些被标记的癌细胞从中间层向表面迁移。对放射自显影片的形态计量分析显示，中间层的小细胞向上迁移并产生粘蛋白，在5.5天时变成成熟的印戒细胞。在15天时，表层中大多数被标记的癌细胞消失。这种细胞更新模式似乎模仿了正常胃黏膜的细胞更新系统。如果癌细胞以这种方式更新，肿瘤必定生长缓慢，在相当长的一段时间内保持为黏膜内癌。
