Mutational signatures of aflatoxin
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ABSTRACT:
PROVIDER: PRJEB20736 | ENA |
REPOSITORIES: ENA
Similar Datasets
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:APOBEC3A induces cancer-specific mutational signatures in human genomes
| PRJEB13145 | ENA
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
2008-05-09 | GSE11382 | 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.
2010-12-07 | GSE25844 | 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
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:Gene expression analysis of A. parasiticus grown under conditions conducive and nonconductive for aflatoxin production was evaluated using glass slide microarrays containing the 753 ESTs. A complex regulatory network governs the biosynthesis of aflatoxin. While several genes involved in aflatoxin production are known, their action alone cannot account for its regulation. Arrays of clones from an Aspergillus flavus cDNA library and glass slide microarrays of ESTs were screened to identify additional genes. An initial screen of the cDNA clone arrays lead to the identification of 753 unique ESTs. Many showed sequence similarity to known metabolic and regulatory genes; however, no function could be ascribed to over 50% of the ESTs. Gene expression analysis of Aspergillus parasiticus grown under conditions conducive and non-conductive for aflatoxin production was evaluated using glass slide microarrays containing the 753 ESTs. Twenty-four genes were more highly expressed during aflatoxin biosynthesis and 18 genes were more highly expressed prior to aflatoxin biosynthesis. No predicted function could be ascribed to 18 of the 24 genes whose elevated expression was associated with aflatoxin biosynthesis. Keywords = Aspergillus Keywords = aflatoxin Keywords: time-course
2003-01-15 | GSE204 | 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, 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.
| S-EPMC5580708 | biostudies-literature
Project description:Gene expression analysis of A. parasiticus grown under conditions conducive and nonconductive for aflatoxin production was evaluated using glass slide microarrays containing the 753 ESTs. A complex regulatory network governs the biosynthesis of aflatoxin. While several genes involved in aflatoxin production are known, their action alone cannot account for its regulation. Arrays of clones from an Aspergillus flavus cDNA library and glass slide microarrays of ESTs were screened to identify additional genes. An initial screen of the cDNA clone arrays lead to the identification of 753 unique ESTs. Many showed sequence similarity to known metabolic and regulatory genes; however, no function could be ascribed to over 50% of the ESTs. Gene expression analysis of Aspergillus parasiticus grown under conditions conducive and non-conductive for aflatoxin production was evaluated using glass slide microarrays containing the 753 ESTs. Twenty-four genes were more highly expressed during aflatoxin biosynthesis and 18 genes were more highly expressed prior to aflatoxin biosynthesis. No predicted function could be ascribed to 18 of the 24 genes whose elevated expression was associated with aflatoxin biosynthesis. Keywords = Aspergillus Keywords = aflatoxin Keywords: time-course
2003-01-15 | E-GEOD-204 | biostudies-arrayexpress
Project description:Aflatoxin is a toxic secondary metabolite produced by the fungi Aspergillus flavus and A. parasiticus. Ingredients of livestock and poultry feed are often contaminated with aflatoxin. Aflatoxin affects many species including humans, dogs, cats, pigs, cattle, and poultry, with liver being the major organ affected. A chicken model was used to evaluate the effect of aflatoxin on hepatic gene expression. Seventy five day-old male broiler chicks were assigned to three dietary treatments (5 replicates of 5 chicks each) from hatch to day 21. The diets contained 0, 1 and 2 mg/kg aflatoxin/kg of feed. Feed intake, body weight gain, liver weights and serum chemistry were evaluated at the end of the study and liver samples were collected in RNase free tubes and stored at -80 ºC. Aflatoxin reduced (P ≤ 0.05) feed intake, body weight, serum total proteins, serum calcium and phosphorus but increased (P < 0.01) liver weights in a dose dependent manner. Microarray experiments were conducted using chicken long oligo arrays, to identify the changes in hepatic gene expression in chicks fed 0 (control) and 2mg/kg aflatoxin/kg of feed. A loop design was followed for microarray experiments with three technical and four biological replicates per treatment group. RNA was extracted from liver tissue and its quality was determined using gel electrophoresis. High quality RNA was purified from DNA contamination, reverse transcribed to cDNA and was used for microarray hybridizations. Microarray data was analyzed using a 2-step ANOVA model using GenePix and MAANOVA softwares, and the differentially expressed genes were identified using SAM, TIGR, and Cluster softwares. The microarray data was validated using real time PCR. It is hypothesized that genes associated with antioxidant, detoxification and immune systems were downregulated and the genes involved in cell proliferation were up-regulated in birds fed aflatoxin compared to controls Keywords: aflatoxin, chicken liver, microarrays, gene expression
2007-07-31 | GSE8603 | GEO