Cova L, Wild C P, Mehrotra R, Turusov V, Shirai T, Lambert V, Jacquet C, Tomatis L, Trépo C, Montesano R
INSERM Unité U 271, International Agency for Research on Cancer, Lyon, France.
Cancer Res. 1990 Apr 1;50(7):2156-63.
The study of two major risk factors in the development of hepatocellular carcinoma, namely persistent hepatitis virus infection and exposure to dietary aflatoxins, has been hampered by lack of an experimental system. To this end we have used a Pekin duck model to examine the effect of congenital duck hepatitis B virus (DHBV) infection and aflatoxin B1 (AFB1) exposure in the induction and development of liver cancer. AFB1 was administered to DHBV infected or noninfected ducks at two doses (0.08 and 0.02 mg/kg) by i.p. injection once a week from the third month posthatch until they were sacrificed (2.3 years later). Two control groups of ducks not treated with AFB1 (one of which was infected with DHBV) were observed for the same period. Each experimental group included 13-16 ducks. Higher mortality was observed in ducks infected with DHBV and treated with AFB1 compared to noninfected ducks treated with AFB1 and other control ducks. In the groups of noninfected ducks treated with high and low doses of AFB1, liver tumors developed in 3 of 10 and 2 of 10 ducks; in infected ducks treated with the high dose 3 of 6 liver tumors were observed and none in the low dose of AFB1. No liver tumors were observed in the two control groups. Ducks infected with DHBV and treated with AFB1 showed more pronounced periportal inflammatory changes, fibrosis, and focal necrosis compared to other groups. All DHBV carrier ducks showed persistent viremia throughout the observation period. An increase of viral DNA titers in livers and sera of AFB1 treated animals compared to infected controls was frequently observed. No DHBV DNA integration into the host genome was observed, although in one hepatocellular carcinoma from an AFB1 treated duck, an accumulation of viral multimer DNA forms was detected. The metabolism of AFB1 in infected and noninfected duck liver was also examined. The study on the role of DHBV infection and AFB1 in the etiopathogenesis of liver tumors may help to clarify some of the basic mechanisms of carcinogenesis.
肝细胞癌发生发展过程中的两个主要危险因素，即持续性肝炎病毒感染和接触膳食黄曲霉毒素，其研究因缺乏实验系统而受阻。为此，我们使用北京鸭模型来研究先天性鸭乙型肝炎病毒（DHBV）感染和黄曲霉毒素B1（AFB1）暴露在肝癌诱导和发展中的作用。从孵化后第三个月开始，每周一次通过腹腔注射，以两种剂量（0.08和0.02mg/kg）给感染或未感染DHBV的鸭子施用AFB1，直至它们被处死（2.3年后）。观察两个未用AFB1处理的鸭对照组（其中一组感染了DHBV）相同的时间段。每个实验组包括13 - 16只鸭子。与未感染DHBV但用AFB1处理的鸭子和其他对照组相比，感染DHBV并用AFB1处理的鸭子死亡率更高。在未感染DHBV且用高剂量和低剂量AFB1处理的组中，10只鸭子分别有3只和2只发生肝肿瘤；在感染DHBV且用高剂量AFB1处理的组中，6只鸭子有3只发生肝肿瘤，而用低剂量AFB1处理的组中未观察到肝肿瘤。两个对照组均未观察到肝肿瘤。与其他组相比，感染DHBV并用AFB1处理的鸭子门静脉周围炎症变化、纤维化和局灶性坏死更为明显。所有DHBV携带鸭在整个观察期内均表现出持续性病毒血症。与感染对照组相比，经常观察到AFB1处理动物的肝脏和血清中病毒DNA滴度增加。未观察到DHBV DNA整合到宿主基因组中，尽管在一只来自AFB1处理鸭的肝细胞癌中，检测到病毒多聚体DNA形式的积累。还研究了感染和未感染鸭肝脏中AFB1的代谢情况。关于DHBV感染和AFB1在肝肿瘤病因发病机制中的作用的研究可能有助于阐明一些致癌的基本机制。
