Uchida T, Suzuki K, Esumi M, Arii M, Shikata T
1st Department of Pathology, Nihon University School of Medicine, Tokyo, Japan.
Cancer Res. 1988 Mar 15;48(6):1559-65.
In an attempt to determine the effect of aflatoxin B1 (AFB) intoxication on livers with duck hepatitis B virus (DHBV) infection, domestic ducks were given 0.1 mg of AFB/kg body weight twice a week for a maximum period of 54 weeks employing various experimental designs. The ducks were infected with DHBV by i.v. inoculation of DHBV-positive sera within 24 h posthatch. The livers were examined histologically, immunohistochemically, and ultrastructurally, and the livers and sera were examined by molecular hybridization for DHBV DNA. AFB administration induced hepatocellular necrosis and marked biliary cell proliferation of the periportal areas, and finally liver cirrhosis. On short-term administration, the hepatocytes of DHBV-infected livers revealed a marked increase in incomplete particles of DHBV by immunostaining and electron microscopy, as compared to those without its administration. Long-term AFB administration provoked frequent nodular or cirrhotic changes. There was no significant increase in frequency of these changes in DHBV-positive ducks as compared to DHBV-negative ones. AFB administration induced hepatocellular carcinoma (HCC) in one DHBV-positive duck and in two DHBV-negative ducks. The HCC and cirrhotic livers revealed extrachromosomal but no integrated form of DHBV DNA by Southern blot hybridization analysis. Immunostaining demonstrated a heterogeneous distribution of DHBV from area to area in nodular and cirrhotic livers. Thus, AFB intoxication provoked various liver disorders independent of DHBV infection, and neither a cocarcinogenic effect of AFB and DHBV nor integration of viral DNA into the genome of neoplastic and nonneoplastic tissues was observed in the present experiments. Generally speaking, DHBV infection did not appear to accelerate hepatic disorders induced by AFB intoxication. However, AFB administration altered the DHBV in the liver in terms of its amount and distribution.
为了确定黄曲霉毒素B1（AFB）中毒对感染鸭乙型肝炎病毒（DHBV）的肝脏的影响，采用各种实验设计，给家鸭每周两次注射0.1毫克AFB/千克体重，最长持续54周。雏鸭在孵化后24小时内通过静脉接种DHBV阳性血清感染DHBV。对肝脏进行组织学、免疫组织化学和超微结构检查，并通过分子杂交检测肝脏和血清中的DHBV DNA。给予AFB可导致肝细胞坏死和门静脉周围区域明显的胆管细胞增殖，最终发展为肝硬化。短期给药时，与未给药的鸭相比，感染DHBV的肝脏中的肝细胞通过免疫染色和电子显微镜检查显示DHBV不完全颗粒明显增加。长期给予AFB会引发频繁的结节性或肝硬化改变。与DHBV阴性鸭相比，DHBV阳性鸭中这些改变的频率没有显著增加。给予AFB在一只DHBV阳性鸭和两只DHBV阴性鸭中诱发了肝细胞癌（HCC）。通过Southern印迹杂交分析，HCC和肝硬化肝脏显示出DHBV DNA的染色体外形式，但没有整合形式。免疫染色显示结节性和肝硬化肝脏中DHBV在不同区域的分布不均一。因此，AFB中毒引发了各种与DHBV感染无关的肝脏疾病，并且在本实验中未观察到AFB和DHBV的协同致癌作用，也未观察到病毒DNA整合到肿瘤组织和非肿瘤组织的基因组中。一般来说，DHBV感染似乎并未加速AFB中毒引起的肝脏疾病。然而，给予AFB在数量和分布方面改变了肝脏中的DHBV。
