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肝细胞癌患者涂片肿瘤组织中的黄曲霉毒素B1 DNA加合物。

Aflatoxin B1 DNA adducts in smeared tumor tissue from patients with hepatocellular carcinoma.

作者信息

Chen C J, Zhang Y J, Lu S N, Santella R M

机构信息

Institute of Public Health, National Taiwan University College of Medicine, Taipei.

出版信息

Hepatology. 1992 Nov;16(5):1150-5.

PMID:1385290
Abstract

Aflatoxins are well-known animal hepatocarcinogens, but the association between aflatoxins and human hepatocellular carcinoma remains to be elucidated. A study method consisting of indirect immunofluorescence assay combined with densitometry was developed to quantitate aflatoxin B1 DNA adducts in smeared liver tissue obtained at the time of biopsy for diagnosis in 50 hepatocellular carcinoma patients in Taiwan. Monoclonal antibody 6A10, generated against the persistent form of the major N7 guanine adduct of aflatoxin B1, was used for detection of adduct. Thirty-five (70%) of the hepatocellular carcinoma samples had detectable levels of aflatoxin B1 DNA adducts (> or = 1/10(6) nucleotides). The detection rate was slightly lower in men (69%) than in women (75%), and younger patients had a significantly higher rate of adducts (83%) than did older ones (58%). Carriers of both HBsAg and HBeAg, carriers of HBsAg only and noncarriers had different rates of detection: 29%, 74% and 82%, respectively. Patients with family histories of hepatocellular carcinoma had a higher detection rate (100%) than did those patients without such histories (67%). No association was found between aflatoxin B1 DNA adducts in liver tissue and Child's score for severity of liver disease. The results suggest that aflatoxin B1 may be involved in the pathogenesis of hepatocellular carcinoma in Taiwan. Our immunohistochemical method for analysis of adducts in small numbers of cells from the target organ should improve results of monitoring for the biologically effective dose of aflatoxin.

摘要

黄曲霉毒素是著名的动物肝癌致癌物,但黄曲霉毒素与人类肝细胞癌之间的关联仍有待阐明。我们开发了一种由间接免疫荧光测定法结合光密度测定法组成的研究方法,用于定量台湾50例肝细胞癌患者活检诊断时获取的肝脏涂片组织中的黄曲霉毒素B1 DNA加合物。针对黄曲霉毒素B1主要N7鸟嘌呤加合物的持续形式产生的单克隆抗体6A10用于检测加合物。35份(70%)肝细胞癌样本检测到黄曲霉毒素B1 DNA加合物水平(≥1/10⁶核苷酸)。男性的检测率(69%)略低于女性(75%),年轻患者的加合物率(83%)显著高于老年患者(58%)。同时携带HBsAg和HBeAg者、仅携带HBsAg者和非携带者的检测率不同,分别为29%、74%和82%。有肝细胞癌家族史的患者检测率(100%)高于无此类家族史的患者(67%)。未发现肝脏组织中的黄曲霉毒素B1 DNA加合物与肝病严重程度的Child评分之间存在关联。结果表明,黄曲霉毒素B1可能参与台湾肝细胞癌的发病机制。我们用于分析靶器官少量细胞中加合物的免疫组织化学方法应能改善黄曲霉毒素生物有效剂量监测的结果。

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Aflatoxin B1 DNA adducts in smeared tumor tissue from patients with hepatocellular carcinoma.肝细胞癌患者涂片肿瘤组织中的黄曲霉毒素B1 DNA加合物。
Hepatology. 1992 Nov;16(5):1150-5.
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Molecular dosimetry of aflatoxin-N7-guanine in human urine obtained in The Gambia, West Africa.西非冈比亚地区采集的人类尿液中黄曲霉毒素 - N7 - 鸟嘌呤的分子剂量测定。
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Chronic hepatitis B carriers with null genotypes of glutathione S-transferase M1 and T1 polymorphisms who are exposed to aflatoxin are at increased risk of hepatocellular carcinoma.谷胱甘肽S-转移酶M1和T1基因多态性呈无效基因型的慢性乙型肝炎携带者,若接触黄曲霉毒素,患肝细胞癌的风险会增加。
Am J Hum Genet. 1996 Jul;59(1):128-34.