Hepatitis B virus x gene and cyanobacterial toxins promote aflatoxin B1-induced hepatotumorigenesis in mice

• Published in: World journal of gastroenterology : WJG 2006-05, Vol.12 (19), p.3065-3072
• Main Authors: Lian, Min, Liu, Ying, Yu, Shun-Zhang, Qian, Geng-Sun, Wan, Shu-Guang, Dixon, Kenneth-R
• Format: Article
• Language: English
• Subjects: Aflatoxin B1 - pharmacology; Animals; Bacterial Toxins - pharmacology; Carcinoma, Hepatocellular - chemically induced; Carcinoma, Hepatocellular - genetics; Carcinoma, Hepatocellular - pathology; Cell Transformation, Neoplastic - drug effects; Cell Transformation, Neoplastic - genetics; Cell Transformation, Neoplastic - pathology; Dose-Response Relationship, Drug; Drug Synergism; Liver Neoplasms - chemically induced; Liver Neoplasms - genetics; Liver Neoplasms - pathology; Male; Marine Toxins - pharmacology; Mice; Mice, Transgenic; Microcystins; Peptides, Cyclic - pharmacology; Poisons - pharmacology; Polymerase Chain Reaction; Rapid Communication; Time Factors; Trans-Activators - genetics; 乙型病毒肝炎; 病理机制; 肝疾病; 黄曲霉毒素
• ISSN: 1007-9327; 2219-2840
• DOI: 10.3748/wjg.v12.i19.3065

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.