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人类结肠中黏膜特异性DNA加合物的存在:对结直肠癌的可能影响。

Presence of mucosa-specific DNA adduct in human colon: possible implication for colorectal cancer.

作者信息

Umemoto A, Kajikawa A, Tanaka M, Hamada K, Seraj M J, Kubota A, Nakayama M, Kinouchi T, Ohnishi Y, Yamashita K

机构信息

Second Department of Surgery, School of Medicine, University of Tokushima, Japan.

出版信息

Carcinogenesis. 1994 May;15(5):901-5. doi: 10.1093/carcin/15.5.901.

DOI:10.1093/carcin/15.5.901
PMID:8200093
Abstract

DNA of normal mucosa and the adjacent muscular layer from 18 adults suffering from colorectal neoplasms was examined by 32P-post-labeling analysis in order to estimate the exposure of the human colon and rectum to environmental carcinogens. Colorectal DNA samples obtained from six newborns were also examined as a normal control because they were presumed to have been minimally exposed to environmental carcinogens. One common mucosa-specific DNA adduct was found in the normal colorectal wall in all adults at the level of 0.10-34.13 adducts/10(8) nucleotides (mean +/- SD: 3.64 +/- 7.92 adducts/10(8) nucleotides), however, these were absent from the newborns' colons. Although several common spots were present in the mucosa, muscular layer and newborn tissues, there was no muscular layer-specific DNA adduct. The relationship between the levels of the mucosa-specific DNA adduct in the non-cancerous part and the histological degree of malignancy was not significant. The presence of this mucosa-specific DNA adduct in adult colon suggests that the human colon is commonly exposed mainly to one environmental carcinogen. This carcinogen is supposed to originate from foods, because the incidence of colorectal carcinoma is closely linked to dietary habits and the mucosa-specific DNA adduct was not present in newborns who had never ingested food. The incidence of adult colonic cancer originating from its mucosa is high, while cases of muscular origin or in newborn colon are rare. Therefore, the mucosa-specific DNA adduct is presumably responsible for the development of colonic cancer of epithelial origin.

摘要

对18名患有结直肠肿瘤的成年人的正常黏膜及相邻肌层的DNA进行了³²P后标记分析,以评估人类结肠和直肠对环境致癌物的暴露情况。还检查了从6名新生儿获得的结直肠DNA样本作为正常对照,因为推测他们极少暴露于环境致癌物。在所有成年人的正常结直肠壁中均发现一种常见的黏膜特异性DNA加合物,其水平为0.10 - 34.13个加合物/10⁸核苷酸(平均值±标准差:3.64±7.92个加合物/10⁸核苷酸),然而,新生儿的结肠中未发现这些加合物。尽管在黏膜、肌层和新生儿组织中有几个常见斑点,但没有肌层特异性DNA加合物。非癌部位黏膜特异性DNA加合物水平与组织学恶性程度之间的关系不显著。成年结肠中这种黏膜特异性DNA加合物的存在表明,人类结肠通常主要暴露于一种环境致癌物。这种致癌物推测源于食物,因为结直肠癌的发病率与饮食习惯密切相关,且从未摄入食物的新生儿中不存在黏膜特异性DNA加合物。起源于黏膜的成年结肠癌发病率高,而起源于肌层或新生儿结肠的病例罕见。因此,黏膜特异性DNA加合物可能是上皮源性结肠癌发生的原因。

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Presence of mucosa-specific DNA adduct in human colon: possible implication for colorectal cancer.人类结肠中黏膜特异性DNA加合物的存在:对结直肠癌的可能影响。
Carcinogenesis. 1994 May;15(5):901-5. doi: 10.1093/carcin/15.5.901.
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Mucosa-specific DNA adducts in human small intestine: a comparison with the colon.
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Exposure to meat-derived carcinogens and bulky DNA adduct levels in normal-appearing colon mucosa.正常外观结肠黏膜中肉类衍生致癌物暴露与大分子DNA加合物水平
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