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乙型肝炎病毒感染与黄曲霉毒素暴露在肝细胞癌发生发展中的相互作用:一种分子流行病学方法。

Interactions between hepatitis B virus infection and exposure to aflatoxins in the development of hepatocellular carcinoma: a molecular epidemiological approach.

作者信息

Sylla A, Diallo M S, Castegnaro J, Wild C P

机构信息

Institut de Recherche Biologique Applique de Guinee (IRBAG), Kindia, Guinea.

出版信息

Mutat Res. 1999 Jul 16;428(1-2):187-96. doi: 10.1016/s1383-5742(99)00046-0.

Abstract

Aflatoxins and hepatitis B virus (HBV) are major risk factors for hepatocellular carcinoma (HCC) in high incidence areas for this cancer, namely southeast Asia and parts of Africa. There is evidence from both epidemiological studies and animal models that the two factors can act synergistically to increase the risk of HCC. The cellular and molecular mechanism of the interaction between these two factors is as yet undefined. However, one possible mechanism attested to by studies in HBV transgenic mice is that chronic liver injury alters the expression of specific carcinogen metabolising enzymes thus modulating the binding of aflatoxin to DNA in hepatocytes. The high levels of aflatoxin exposure which occur in many areas of the world where chronic HBV infection is endemic indicate that measures to reduce aflatoxin exposure would contribute to reducing HCC incidence. In preliminary studies, Guinea-Conakry have established baseline data for the implementation of a community-based intervention study to evaluate the effectiveness of improved post-harvest processing and storage of the groundnut crop, a major source of aflatoxins. Aflatoxin-albumin adducts were measured in 423 sera from individuals living in the four natural geographic zones of Guinea. More than 95% of the serum samples were positive for this biomarker and highest exposures were found in Lower Guinea where groundnuts are consumed as a dietary staple. Variations in mean levels between villages within a geographic region did not vary greatly. HBV infection was endemic in all regions with an overall prevalence of 16.7% chronic carriers. Thus in this population both HBV vaccination and reduction in aflatoxin exposure would be beneficial in decreasing morbidity and mortality from liver disease.

摘要

黄曲霉毒素和乙型肝炎病毒(HBV)是肝癌高发地区(即东南亚和非洲部分地区)肝细胞癌(HCC)的主要危险因素。流行病学研究和动物模型均有证据表明,这两种因素可协同作用增加肝细胞癌风险。这两种因素之间相互作用的细胞和分子机制尚不明确。然而,在HBV转基因小鼠中的研究证实了一种可能的机制,即慢性肝损伤会改变特定致癌物代谢酶的表达,从而调节黄曲霉毒素与肝细胞中DNA的结合。在慢性HBV感染流行的世界许多地区,黄曲霉毒素暴露水平很高,这表明减少黄曲霉毒素暴露的措施将有助于降低肝细胞癌的发病率。在初步研究中,几内亚-科纳克里已经建立了基线数据,以实施一项基于社区的干预研究,评估改进花生作物收获后加工和储存(黄曲霉毒素的主要来源)的有效性。对来自几内亚四个自然地理区域居民的423份血清进行了黄曲霉毒素-白蛋白加合物检测。超过95%的血清样本对该生物标志物呈阳性,在以花生为主食的下几内亚发现黄曲霉毒素暴露水平最高。一个地理区域内不同村庄的平均水平差异不大。HBV感染在所有地区均呈地方性流行,慢性携带者的总体患病率为16.7%。因此,在这一人群中,接种HBV疫苗和减少黄曲霉毒素暴露都将有助于降低肝病的发病率和死亡率。

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