Liver and cecum from mice exposed to aflatoxin B1 (AFB1) and/or Helicobacter hepaticus
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE11382 | GEO | 2008/05/09
SECONDARY ACCESSION(S): PRJNA106497
REPOSITORIES: GEO
Similar Datasets
Project description:We evaluated aflatoxin B1-induced liver tumor promotion by H. hepaticus. Microarrays of liver and cecum from female mice were used to evaluate the individual and combined transcriptional effects of AFB1 and H. hepaticus Experiment Overall Design: C3H/HeN mice were inoculated with 7 ug/g BW AFB1 or vehicle IP at 10 days of age, and gavaged with H. hepaticus or broth at 3 weeks; necropsied at 40 weeks
2008-06-20 | E-GEOD-11382 | biostudies-arrayexpress
Project description:Applied de novo assembly, both protein coding and non-coding RNAs were profiled in AFB1 induced HCC and AFB1 resistant liver sample. Compared with normal liver, the perturbation on transcriptome was revealed in multiple aspects, implying the potential mechanism of toxic resistance.
2016-01-20 | GSE70097 | GEO
Project description:Applied de novo assembly, both protein coding and non-coding RNAs were profiled in AFB1 induced HCC and AFB1 resistant liver sample. Compared with normal liver, the perturbation on transcriptome was revealed in multiple aspects, implying the potential mechanism of toxic resistance. All rats were randomly divided into control and treated groups according to their weight. Then AFB1 was injected intraperitoneally to treated group in customized schedule. Biopsy was applied every 10 weeks on both groups. Tissues from rats died of HCC were reserved. All rats were sacrificed at 70th week. According to whether tumor formed, liver tissues from animals in treated group were further divided into AFB1 induced tumor sample and AFB1 resistant sample. Both samples were stored for later transcriptome analysis, as well as the normal sample from control group. RNA profiles of all 3 samples were generated by deep sequencing, using Illumina HiSeq2000 platform.
2016-01-20 | E-GEOD-70097 | biostudies-arrayexpress
Project description:Liver and cecum from mice exposed to aflatoxin B1 (AFB1) and/or Helicobacter hepaticus
| PRJNA106497 | ENA
Project description: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. HCV transgenic mice (SL-139 strain, pAlbSVPA-HCV-S, containing the structural genes core, E1, E2, and p7, nucleotides 342-2771 of HCV genotype 1b, strain N, under the control of the murine albumin promoter/enhancer) on C57BL/6J (Jackson Laboratory, Bar Harbor, ME) background were previously reported in Lerat et al (Lerat et al., Gastroenterology 122, 352-365, 2002). Transgenic animals were identified after weaning as detailed in Korenaga et al (Korenaga et al., J Biol. Chem. 280, 37481-37488, 2005). Neonatal (7 days old) mice were administered a single dose of AFB1 (6 ug/g bw) or tricaprylin vehicle (15 ul/g bw) by intra-peritoneal injection. Male mice were maintained on the regular animal chow with free access to food and water for up to 12 months. All animal experiments were approved by the UNC Animal Care and Use Committee. There were 20 liver samples used for microarray analysis (12 month time point). All samples were run in one batch. There are 4 groups: WT/Control (4 samples - all biological replicates, i.e., different animals); WT/AFB1 (6 samples); HCV/Control (4 samples); HCV/AFB1 (6 samples). This was a 2 color design with a common reference mRNA. No dye swaps or replicate arrays were included.
2011-01-25 | E-GEOD-26838 | biostudies-arrayexpress
Project description:Comparison of gene expression profiles induced by the mycotoxin, aflatoxin B1 (AFB1), in primary human hepatocytes and HepaRG cells. Initial mechanisms involved in the complex multistep process leading to malignant transformation by chemicals remain largely unknown. We have analysed changes in gene expression profiles in primary human hepatocytes and differentiated human hepatoma HepaRG cells after a 24 h treatment with 0.05 or 0.25µM aflatoxin B1 (AFB1), a potent genotoxic hepatocarcinogen.
2010-12-07 | GSE25844 | GEO
Project description: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. HCV transgenic mice (SL-139 strain, pAlbSVPA-HCV-S, containing the structural genes core, E1, E2, and p7, nucleotides 342-2771 of HCV genotype 1b, strain N, under the control of the murine albumin promoter/enhancer) on C57BL/6J (Jackson Laboratory, Bar Harbor, ME) background were previously reported in Lerat et al (Lerat et al., Gastroenterology 122, 352-365, 2002). Transgenic animals were identified after weaning as detailed in Korenaga et al (Korenaga et al., J Biol. Chem. 280, 37481-37488, 2005). Neonatal (7 days old) mice were administered a single dose of AFB1 (6 ug/g bw) or tricaprylin vehicle (15 ul/g bw) by intra-peritoneal injection. Male mice were maintained on the regular animal chow with free access to food and water for up to 12 months. All animal experiments were approved by the UNC Animal Care and Use Committee.
2011-01-25 | GSE26838 | GEO
Project description:Aflatoxin B1 (AFB1) is a mutagen and IARC (International Agency for Research on Cancer) Group 1 carcinogen that causes hepatocellular carcinoma (HCC). Here we present the first whole genome data on the mutational signatures of AFB1 exposure from a total of > 40,000 mutations in four experimental systems: two different human cell lines, and in liver tumors in wild-type mice and in mice that carried a hepatitis B surface antigen transgene – this to model the multiplicative effects of aflatoxin exposure and hepatitis B in causing HCC. AFB1 mutational signatures from all four experimental systems were remarkably similar. We integrated the experimental mutational signatures with data from newly-sequenced HCCs from Qidong County, China, a region of well-studied aflatoxin exposure. This indicated that COSMIC mutational signature 24, previously hypothesized to stem from aflatoxin exposure, indeed likely represents AFB1 exposure, possibly combined with other exposures. Among published somatic mutation data, we found evidence of AFB1 exposure in 0.7% of HCCs treated in North America, 1% of HCCs from Japan, but 16% of HCCs from Hong Kong. Thus, aflatoxin exposure apparently remains a substantial public health issue in some areas. This aspect of our study exemplifies the promise of future widespread resequencing of tumor genomes in providing new insights into the contribution of mutagenic exposures to cancer incidence.
| EGAS00001002490 | EGA
Project description:Aflatoxin B1 (AFB1), a potent carcinogenic mycotoxin, is known to contribute to liver cancer development. Within the cell, bioactivated AFB1 intercalates into the DNA double helix, forming bulky DNA adducts that lead to mutagenesis if left unrepaired. Here, we adapted the tXR-seq method to map the nucleotide excision repair of AFB1-induced DNA lesions at genome-wide level. Our research uncovered that transcription-coupled repair plays a major role in repairing the AFB1-induced DNA lesions. We identified a distinctive length distribution pattern for the excision products released during repair, suggesting a unique dual incision mechanism for AFB1-induced DNA lesions. Notably, we revealed that repair activity is more pronounced on chromosomes closer to the nuclear center and A compartments undergo faster repair compared with B compartments. Additionally, we observed higher repair activity within regions encompassing TAD boundaries and loop anchors. This study provides insights into the interplay between repair, transcription, and 3D genome organization, shedding light on the mechanisms behind AFB1-associated liver cancer development.
2023-10-19 | GSE243425 | GEO
Project description:Comparison of gene expression profiles induced by the mycotoxin, aflatoxin B1 (AFB1), in primary human hepatocytes and HepaRG cells. Initial mechanisms involved in the complex multistep process leading to malignant transformation by chemicals remain largely unknown. We have analysed changes in gene expression profiles in primary human hepatocytes and differentiated human hepatoma HepaRG cells after a 24 h treatment with 0.05 or 0.25µM aflatoxin B1 (AFB1), a potent genotoxic hepatocarcinogen. Three independent biological replicates of HepaRG cell cultures and two pools of three primary human hepatocyte cultures each, were investigated. Cells were treated with 0.05 or 0.25µM AFB1 for 24 h.
2010-12-07 | E-GEOD-25844 | biostudies-arrayexpress