Hepatitis B virus x gene and cyanobacterial toxins promote aflatoxin B_1-induced hepatotumorigenesis in mice  

作　　者：Min Lian Ying Liu Shun-Zhang Yu Geng-Sun Qian Shu-Guang Wan Kenneth R Dixon 

机构地区：[1]School of Public Health, Fudan University, 138 Yixueyuan Road, Shanghai 200032, China Geng-Sun Qian, Shu-Guang Wan, Shanghai Cancer Institute, Shanghai 200032, China [2]Shanghai Cancer Institute, Shanghai 200032, China [3]Institute of Environmental and Human Health, Texas Tech University and TTU Health Sciences Center, Lubbock, TX, United States

出　　处：《World Journal of Gastroenterology》2006年第19期3065-3072,共8页世界胃肠病学杂志（英文版）

基　　金：Supported by the Key Project of National Natural Science Foundation of China, No. 39730380

摘　　要：AIM： To assess the combinative role of aflatoxin B1 （AFB1）, cyanobacterial toxins （cyanotoxins）, and hepatitis B virus （HBV） x gene in hepatotumorigenicity. METHODS： One-week-old animals carrying HBV x gene and their wild-type littermates were intraperitoneally （ip） injected with either single-dose AFB1 [6 mg/kg body weight （bw）], repeated-dose cyanotoxins （microcystin- LR or nodularin, 10 μg/kg bw once a week for 15 wk）, DMSO （vehicle control） alone, or AFB1 followed by cyanotoxins a week later, and were sacrificed at 24 and 52 wk post-treatment. RESULTS： AFB1 induced liver tumors in 13 of 29 （44.8%） transcjenic mice at 52 wk post-treatment, significantly more frequent than in wild-type mice （13.3%）. This significant difference was not shown in the 24-wk study. Compared with AFB1 exposure alone, MC-LR and nodularin yielded approximately 3-fold and 6-fold increases in the incidence of AFB1-induced liver tumors in wild-type animals at 24 wk, respectively. HBV x gene did not further elevate the risk associated with coexposure to AFB1 and cyanotoxins. With the exception of an MC-LR-dosed wild-type mouse, no liver tumor was observed in mice treated with cyanotoxins alone at 24 wk. Neither DMSO-treated transgenic mice nor their wild-type littermates had pathologic alterations relevant to hepatotumorigenesis in even up to 52 wk. CONCLUSION： HBV x gene and nodularin promote the development of AFB1-induced liver tumors. Co-exposure to AFB1 and MC-LR tends to elevate the risk of liver tumors at 24 wk relative to exposure to one of them. The combinative effect of AFB1, cyanotoxins and HBVx on hepatotumorigenesis is weak at 24 wk.瞄准：估计黄麴毒素的结合的角色 B1 (AFB1 ) ， cyanobacterial 毒素(cyanotoxins ) ，和肝炎 B (HBV ) 在 hepatotumorigenicity 的 x 基因。方法：( ip )带 HBV x 基因和他们的野类型的同窝出生的人的 One-week-old 动物 intraperitoneally 与也被注射单个剂量的 AFB1 [ 6 mg/kg 体重( bw )]，重复剂量 cyanotoxins ( microcystin-LR 或在榴状， 10 microg/kg bw 每周一次为 15 wk )， DMSO (车辆控制)独自一个，或 AFB1 一个星期以后由 cyanotoxins 列在后面，并且在 24 和 52 wk 被牺牲处理以后。结果：AFB1 在 29 中的 13 个导致了肝肿瘤(44.8%) 在 52 wk 的转基因的老鼠处理以后，显著地比在野类型的老鼠(13.3%) 更经常。这有效差量没在 24-wk 学习被显示出。与 AFB1 暴露相比独自一个， MC-LR 并且在榴状在导致的 AFB (1 ) 的发生产出近似 3 褶层和 6 褶层增加在在 24 wk 的野类型的动物的肝肿瘤分别地。HBV x 基因进一步没提高与合作暴露联系到 AFB1 和 cyanotoxins 的风险。与一个 MC-LR-dosed 野类型的鼠标的异常，没有肝肿瘤在在 24 wk 独自与 cyanotoxins 对待的鼠标被观察。既不对待 DMSO 的转基因的老鼠也不他们的野类型的同窝出生的人在甚至多达 52 wk 有与 hepatotumorigenesis 相关的病理学的改变。结论：HBV x 基因并且在榴状支持导致的 AFB (1 ) 的发展肝肿瘤。到 AFB1 和 MC-LR 的合作暴露趋于相对暴露在 24 wk 提高肝肿瘤的风险到他们之一。hepatotumorigenesis 上的 AFB1， cyanotoxins 和 HBVx 的结合的效果在 24 wk 是弱的。

关 键 词：AFLATOXINS CYANOBACTERIA Hepatitis B virus Liver neoplasms Transgenic mice 

分 类 号：R512.62[医药卫生—内科学]