Rubio Carlos A
Gastrointestinal and Liver Research Laboratory, Department of Pathology, Karolinska Institute and University Hospital, Stockholm, Sweden
Anticancer Res. 2017 May;37(5):2265-2268. doi: 10.21873/anticanres.11563.
The colonic crypts in rats replicate by symmetric fission at the base of the crypts, and proceeds upwards, to generate two separate identical crypts. Recently, anomalous crypts (called corrupted colonic crypts, CCCs) were found in the colonic mucosa of Sprague-Dawley rats treated with the carcinogen dimethylhydrazine. Here it was investigated whether CCCs develop in the colonic mucosa of another rat strain, treated with a different carcinogen.
Archived Swiss-roll colon sections from 25 male Fisher-344 rats treated with the mutagen 2-amino-6-methyldipyrido imidazole (GLU1) were reviewed. Non-dysplastic and dysplastic CCCs were regarded as those exhibiting asymmetric fission, asymmetric lateral sprouting/lateral fission, basal dilatations, or spatial aberrations of the normal (vertical) axis. Colonic adenomas were found in three out of the 25 specimens.
In the entire colonic mucosa of the 25 GLU1-treated rats, 130 non-dysplastic CCCs were recorded amongst 357 non-dysplastic crypts with fission (36.4%). The mean number of non-dysplastic CCCs per animal was 5.2 (range=2-12). These numbers only mirror events taking place at a particular time (i.e. at sacrifice). Considering the high cell production rate of the colonic crypts, the actual number of CCCs/rat occurring during the usual mucosal turnover time of 72 hours might be substantial. In the three adenoma specimens, non-dysplastic CCCs were found underneath CCCs with dysplasia.
For many years, the development of crypt dysplasia and adenoma have been considered the initial histological events in colonic carcinogenesis. This study demonstrates that non-dysplastic CCCs also develop in GLU 1-treated Fisher-344 rats. Non-dysplastic CCCs were found underneath CCCs with dysplasia. Non-dysplastic CCCs might act as scaffolds at the time of top-down cell replacement/transformation of the crypts by dysplastic cells. It is submitted that non-dysplastic CCCs might be the initial histological recordable event in experimental colonic carcinogenesis.
大鼠结肠隐窝通过隐窝底部的对称裂变进行复制，并向上发展，形成两个独立的相同隐窝。最近，在用致癌物二甲基肼处理的斯普拉格 - 道利大鼠的结肠黏膜中发现了异常隐窝（称为腐败结肠隐窝，CCCs）。在此研究了用不同致癌物处理的另一品系大鼠的结肠黏膜中是否会出现CCCs。
回顾了25只经诱变剂2 - 氨基 - 6 - 甲基二吡啶并咪唑（GLU1）处理的雄性费希尔 - 344大鼠的存档瑞士卷结肠切片。非发育异常和发育异常的CCCs被视为表现出不对称裂变、不对称侧向发芽/侧向裂变、基底扩张或正常（垂直）轴的空间畸变的隐窝。在25个标本中有3个发现了结肠腺瘤。
在25只经GLU1处理的大鼠的整个结肠黏膜中，在357个有裂变的非发育异常隐窝中记录到130个非发育异常的CCCs（36.4%）。每只动物非发育异常CCCs的平均数量为5.2（范围 = 2 - 12）。这些数字仅反映了在特定时间（即处死时）发生的事件。考虑到结肠隐窝的高细胞产生率，在通常的72小时黏膜更新时间内每只大鼠实际出现的CCCs数量可能相当可观。在3个腺瘤标本中，在发育异常的CCCs下方发现了非发育异常的CCCs。
多年来，隐窝发育异常和腺瘤的发生一直被认为是结肠致癌过程中的初始组织学事件。本研究表明，在经GLU1处理的费希尔 - 344大鼠中也会出现非发育异常的CCCs。在发育异常的CCCs下方发现了非发育异常的CCCs。在发育异常细胞自上而下替换/转化隐窝时，非发育异常的CCCs可能起到支架作用。有人认为，非发育异常的CCCs可能是实验性结肠致癌过程中最初可记录的组织学事件。
