Quimby G F, Eastwood G L
J Natl Cancer Inst. 1981 Feb;66(2):331-7.
The effect of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) on gastroduodenal epithelial proliferation p]rior to the development of frank neoplasia was studied in inbred LEW rats with or without gastric ulcers. The rats received either MNNG (100 gm/liter) in the drinking water or plain water. After 4 weeks, some rats in the MNNG-treated and control groups were given injections of tritiated thymidine and killed 1 hour later. In other rats, either an ulcer of the fundic mucosa was formed by a suction biopsy tube at laparotomy or a sham operation was performed. At 2 and 4 weeks after the operation, these rats were given injections of tritiated thymidine and killed 1 hour later. Sections of fundus, antrum, and duodenum were prepared for light autoradiography. MNNG treatment stimulated gastroduodenal epithelial proliferation, expanded the proliferative zone (PZ), and in the duodenum caused marked villus blunting and elongation of the crypts. No additional effect of the fundic ulcer or sham operation on gastroduodenal proliferation could be determined. The MNNG-induced expansion of the PZ occurred in a downward direction. Thus theories of carcinogenesis should include not only the expansion of the PZ toward the mucosal surface but also the possibility of expansion of the PZ toward the base of the mucosa.
在有或没有胃溃疡的近交系LEW大鼠中，研究了N-甲基-N'-硝基-N-亚硝基胍（MNNG）在明显肿瘤形成之前对胃十二指肠上皮增殖的影响。大鼠饮用含MNNG（100克/升）的水或普通水。4周后，给MNNG处理组和对照组的一些大鼠注射氚标记的胸腺嘧啶核苷，并在1小时后处死。在其他大鼠中，通过剖腹手术用吸引活检管形成胃底黏膜溃疡或进行假手术。在手术后2周和4周，给这些大鼠注射氚标记的胸腺嘧啶核苷，并在1小时后处死。制备胃底、胃窦和十二指肠切片用于光镜放射自显影。MNNG处理刺激了胃十二指肠上皮增殖，扩大了增殖区（PZ），并且在十二指肠中导致明显的绒毛变钝和隐窝延长。无法确定胃底溃疡或假手术对胃十二指肠增殖的额外影响。MNNG诱导的PZ扩展是向下发生的。因此，致癌理论不仅应包括PZ向黏膜表面的扩展，还应包括PZ向黏膜底部扩展的可能性。
