McLellan E A, Medline A, Bird R P
Histopathology Unit, Imperial Cancer Research Foundation, London, UK.
Carcinogenesis. 1991 Nov;12(11):2093-8. doi: 10.1093/carcin/12.11.2093.
Foci of aberrant crypts (ACF) have been identified in the unsectioned methylene blue stained rodent colons and hypothesized to represent precursor lesions of colon cancer. In the present study, induction and growth characteristics of ACF were investigated in response to a single injection of varying dosages of 1,2-dimethylhydrazine-2HCl (DMH), a colon carcinogen. Female Sprague-Dawley rats were given a single injection of DMH (5-150 mg/kg). Two and 19 weeks after the injection, animals were killed and their distal 10 cm of colons were enumerated for the number and crypt multiplicity of ACF. Number of ACF increased with increasing dosages of DMH plateauing at 100 mg/kg. However, percentage of ACF exhibiting different crypt multiplicity (1 to greater than 4) were similar among different dose groups. Aberrant crypts and normal crypts were enumerated for total number of cells and number and distribution of S-phase cells along the crypt height 19 weeks after DMH injection after autoradiography. The labeling index (LI) (percentage of S-phase cells) and LI along the crypt height were determined. Compared to the surrounding normal crypts, aberrant crypts exhibited significantly higher (P less than 0.05) number of cells (1122 +/- 81 versus 411 +/- 28) and higher (P less than 0.05) LI (21 +/- 1 versus 12 +/- 1). For the eight ACF analysed in the present study, the distribution of S-phase cells in the aberrant crypts were similar to that of normal crypts in that S-phase cells were restricted to the lower two-thirds of the crypts rather than distributed throughout the height of the crypts as reported for adenomatous epithelium.
在未切片的经亚甲蓝染色的啮齿动物结肠中已发现异常隐窝灶（ACF），并推测其为结肠癌的前体病变。在本研究中，针对单次注射不同剂量的1,2 - 二甲基肼 - 2HCl（DMH，一种结肠致癌物），研究了ACF的诱导和生长特性。给雌性斯普拉格 - 道利大鼠单次注射DMH（5 - 150mg/kg）。注射后2周和19周，处死动物，对其结肠远端10cm进行ACF数量及隐窝多样性计数。ACF数量随DMH剂量增加而增加，在100mg/kg时达到平台期。然而，不同剂量组中显示不同隐窝多样性（1至大于4）的ACF百分比相似。在DMH注射19周后进行放射自显影，对异常隐窝和正常隐窝的细胞总数以及沿隐窝高度的S期细胞数量和分布进行计数。测定标记指数（LI）（S期细胞百分比）及沿隐窝高度的LI。与周围正常隐窝相比，异常隐窝显示出显著更高（P < 0.05）的细胞数量（1122 ± 81对411 ± 28）和更高（P < 0.05）的LI（21 ± 1对12 ± 1）。对于本研究中分析的8个ACF，异常隐窝中S期细胞的分布与正常隐窝相似，即S期细胞局限于隐窝的下三分之二，而非如腺瘤上皮那样分布于隐窝的整个高度。
