DOSE-RESPONSE AND PROLIFERATIVE CHARACTERISTICS OF ABERRANT CRYPT FOCI - PUTATIVE PRENEOPLASTIC LESIONS IN RAT COLON
DOSE-RESPONSE AND PROLIFERATIVE CHARACTERISTICS OF ABERRANT CRYPT FOCI - PUTATIVE PRENEOPLASTIC LESIONS IN RAT COLON
复制标题
DOI：
10.1093/carcin/12.11.2093
复制
发表时间：
1991-11-01
期刊：
影响因子：
4.7
通讯作者：
BIRD, RP
中科院分区：
文献类型：
--
作者：
MCLELLAN, EA;MEDLINE, A;BIRD, RP
异常隐窝病灶(ACF)已经在未切片的亚甲蓝染色的啮齿动物结肠中被发现，并被推测为结肠癌的前驱病变。本文研究了单次注射不同剂量的1，2-二甲基肼-2HCl(DMH)对ACF的诱导和生长特性。雌性SD大鼠单次注射DMH(5~150 mg/kg)。分别于注射后2周和19周处死动物，计数结肠远端10 cm处的ACF数量和隐窝多发性。在100 mg/kg的DMH平台上，ACF数量随DMH剂量的增加而增加。然而，不同剂量组表现出不同隐窝多样性的ACF百分比(1到4)相似。放射自显影后19周，计数畸形隐窝和正常隐窝的细胞总数和S期细胞沿隐窝高度的数量和分布。测定标记指数(LI)(S期细胞的百分比)和LI沿隐窝高度的变化。与周围正常隐窝相比，异常隐窝的细胞数(1122+/-81比411+/-28)和LI(21+/-1比12+/-1)显著增加(P<；0.05)。在本研究中所分析的8例ACF中，S期细胞在异常隐窝中的分布与正常隐窝相似，即S期细胞局限于隐窝的下部2/3，而不是像腺瘤上皮那样分布于整个隐窝的高度。
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 > 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 < 0.05) number of cells (1122 +/- 81 versus 411 +/- 28) and higher (P < 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.