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 Keywords: Tumor co-promotion study
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
Project description:Aflatoxin B1 (AFB1) is a mycotoxin produced by Aspergillus flavus and A. parasiticus. AFB1 targeted gene expression profiles were determined in human primary trophoblast cells, isolated from full term placentae after delivery, and exposed to 1 µM AFB1 for 72 hours. Gene expression profiling conducted with human HT-12 expression beadchips
Project description:Susceptibility to the hepatocarcinogen Aflatoxin B1 (AFB1) varies among species and with age. Mice are refractory to carcinogenic and toxic effects of AFB1; however, B6C3F1 mice show transient sensitivity if dosed shortly after birth. We compared age-related differences in gene expression and transcriptional responses to AFB1 in livers of newborn (4-day-old) and adult mice. Keywords: Transcriptional response to a carcinogen
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.
Project description:We are investigating the transcriptional response of mice infected with Helicobacter hepaticus and links to liver cancer We used microarrays to detail the global programme of gene expression underlying H. hepaticus induced liver cancer Keywords: disease model
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.
Project description:We are investigating the transcriptional response of mice infected with Helicobacter hepaticus and links to liver cancer; We used microarrays to detail the global programme of gene expression underlying H. hepaticus induced liver cancer Experiment Overall Design: Mice with tumors were compared to mice with infection only (comparison 2) and mice infected were compared to control mice (comparison 1)
Project description:Aflatoxin B1 (AFB1) is amongst the mycotoxins commonly affecting human and animal health, raising global food safety and control concerns. The mechanisms underlying AFB1 toxicity are poorly understood. Moreover, antidotes against AFB1 are lacking. Genome-wide CRISPR/Cas9 knockout screening in porcine kidney cells identified the transcription factor BTB and CNC homolog 1 (BACH1) as a gene required for AFB1 toxicity. The inhibition of BACH1 expression in porcine kidney cells and human hepatoma cells resulted in increased resistance to AFB1. BACH1 depletion attenuates AFB1-induced oxidative damage via the upregulation of antioxidant genes.
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.
