Title: Liver effects of Aflatoxin B1 (AFB1) in wild type (C57BL/6J) and hepatitis C virus-transgenic (HCV-Tg) mice

Accession Number: GSE26838

Link to Dataset: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE26838

Repository: Gene Expression Omnibus (GEO)

Data Type(s): Gene Expression

Experiment Type(s): Expression profiling by array

Organism(s): Mus musculus

Summary: Viral hepatitis and aflatoxin B1 (AFB1) exposure are common risk factors for hepatocellular carcinoma (HCC). The incidence of HCC in individuals co-exposed to hepatitis C (HCV) or B virus and AFB1 is greater than could be explained by the additive effect, yet the mechanisms are poorly understood due to lack of an animal model. This study investigated the outcomes and mechanisms of combined exposure to HCV and AFB1. We hypothesized that HCV transgenic (HCV-Tg; expressing core, E1, E2, and p7, nucleotides 342-2771) mice will be prone to hepatocarcinogenesis when exposed to AFB1. Neonatal (7 days old) HCV-Tg or C57BL/6J wild-type mice were exposed to AFB1 (6 ug/g bw) or tricaprylin vehicle (15 ul/g bw) and male offspring were followed for up to 12 months. No liver lesions were observed in vehicle-treated wild type or HCV-Tg mice. Tumors (adenomas or carcinomas) and preneoplastic lesions (hyperplasia or foci) were observed in 22.5% (9 of 40) of AFB1-treated wild-type mice. In HCV-Tg, the incidence of tumorous or pre-tumorous lesions was significantly elevated (50%, 18 of 36), with the difference largely due to a 2.5-fold increase in the incidence of adenomas (30.5% vs 12.5%). While oxidative stress and steato-hepatisis were observed in both AFB1-treated groups, molecular changes indicative of the enhanced inflammatory response and altered lipid metabolism were more pronounced in HCV-Tg mice. In summary, HCV proteins core, E1, E2 and p7 are sufficient to reproduce the additive co-carcinogenic effect of HCV and AFB1 which is a known clinical phenomenon.

Publication(s) associated with this dataset:

• Jeannot E, Boorman GA, Bradford BU, Shymoniak S, Tumurbaatar B, Weinman SA, Melnyk SB, Tryndyak VP, Pogribny IP, Rusyn I, Kosyk O. 2012. Increased incidence of aflatoxin B1-induced liver tumors in hepatitis virus C transgenic mice. Int J Cancer 130(6):1347-1356. doi:10.1002/ijc.26140 PMID:21500192 PMCID:PMC3161148

Project(s) associated with this dataset:

• University of North Carolina-Chapel Hill: Genomic and Genetic Analysis of Liver and Kidney Toxicity of Trichloroethylene