期刊
WORLD JOURNAL OF GASTROENTEROLOGY
卷 12, 期 19, 页码 3065-3072出版社
BAISHIDENG PUBLISHING GROUP INC
DOI: 10.3748/wjg.v12.i19.3065
关键词
aflatoxins; cyanobacteria; hepatitis B virus; liver neoplasms; transgenic mice
AIM: To assess the combinative role of aflatoxin B-1 (AFB(1)), 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 AFB(1) [6 mg/kg body weight (bw)], repeated-dose cyanotoxins (microcystin-LR or nodularin, 10 mu g/kg bw once a week for 15 wk), DMSO (vehicle control) alone, or AFB(1) followed by cyanotoxins a week later, and were sacrificed at 24 and 52 wk post-treatment. RESULTS: AFB(1) induced liver tumors in 13 of 29 (44.8%) transgenic 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 AFB(1) exposure alone, MC-LR and nodularin yielded approximately 3-fold and 6-fold increases in the incidence of AFB(1)-induced liver tumors in wild-type animals at 24 wk, respectively. HBV x gene did not further elevate the risk associated with coexposure to AFB(1) 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 AFB(1)-induced liver tumors. Co-exposure to AFB(1) 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 AFB(1), cyanotoxins and HBVx on hepatotumorigenesis is weak at 24 wk. (c) 2006 The WJG Press. All rights reserved.
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