Division of Internal Medicine, Hepatobiliary and Immunoallergic Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy.
Cesare Maltoni Cancer Research Center, Ramazzini Institute, Via Saliceto 3, 40010 Bentivoglio, Italy.
Nutrients. 2022 Apr 15;14(8):1652. doi: 10.3390/nu14081652.
Aflatoxin B1 (AFB1) is a class 1 carcinogen with an ascertained role in the development of hepatocellular carcinoma (HCC) in high exposure areas. Instead, this study aimed to assay whether chronic/intermittent, low-dose AFB1 consumption might occur in low-exposure geographical areas, ultimately accumulating in the liver and possibly contributing to liver cancer. AFB1-DNA adducts were assayed by immunostaining in liver tissues from three Italian series of twenty cirrhosis without HCC, 131 HCC, and 45 cholangiocarcinoma, and in an AFB1-induced HCC rat model. CD68, TP53 immunostaining, and TP53 RFLP analysis of R249S transversion were used to characterize cell populations displaying AFB1-DNA adducts. Twenty-five HCCs displayed AFB1-adducts both in neoplastic hepatocytes and in cells infiltrating the tumor and non-tumor tissues. Nuclear immunostaining was observed in a few cases, while most cases showed cytoplasmic immunostaining, especially in CD68-positive tumor-infiltrating cells, suggestive for phagocytosis of dead hepatocytes. Similar patterns were observed in AFB1-induced rat HCC, though with higher intensity. Cholangiocarcinoma and cirrhosis without HCC did not displayAFB1-adducts, except for one case. Despite not providing a causal relationship with HCC, these findings still suggest paying attention to detection and control measures for aflatoxins to ensure food safety in low exposure areas.
黄曲霉毒素 B1（AFB1）是一种 1 类致癌物，已确定其在高暴露地区肝细胞癌（HCC）的发展中起作用。相反，本研究旨在检测在低暴露地区是否可能发生慢性/间歇性、低剂量 AFB1 摄入，这种摄入是否会在肝脏中蓄积，并可能导致肝癌。通过免疫染色法检测了来自三个意大利系列的 20 例无 HCC 肝硬化、131 例 HCC 和 45 例胆管癌的肝组织以及 AFB1 诱导的 HCC 大鼠模型中的 AFB1-DNA 加合物。CD68、TP53 免疫染色和 TP53 RFLP 分析用于鉴定显示 AFB1-DNA 加合物的细胞群。25 例 HCC 中均显示出 AFB1 加合物，这些加合物存在于肿瘤性肝细胞和浸润肿瘤及非肿瘤组织的细胞中。少数病例中观察到核免疫染色，而大多数病例显示细胞质免疫染色，尤其是在 CD68 阳性的肿瘤浸润细胞中，提示吞噬了死亡的肝细胞。在 AFB1 诱导的大鼠 HCC 中也观察到类似的模式，但强度更高。胆管癌和无 HCC 的肝硬化除了一例外均未显示 AFB1 加合物。尽管这些发现并未提供与 HCC 之间的因果关系，但仍建议在低暴露地区注意检测和控制黄曲霉毒素的措施，以确保食品安全。
