Paternal Benzo[a]pyrene Exposure Modulates MicroRNA Expression Patterns in the Developing Mouse Embryo

Little attention has been given to how microRNA expression is affected by environmental contaminants exposure. We investigate the effects of paternal exposure to benzo[a]pyrene (B[a]P) on miRNA expression in the developing mouse embryo. Male mice were exposed to B[a]P (150 mg/kg i.p.), and their sperm was used four days later in in-vitro fertilization experiments. Twenty embryos each from 2-, 8-cell and the blastocyst stage were used for genome-wide miRNA expression profiling. Paternal exposure to B[a]P affected the expression of several miRNAs, and the target genes for some of the dysregulated miRNAs were enriched in many different pathways that are likely to be relevant for the developing mouse embryo. By linking the miRNA target genes to publicly available databases, we identified some miRNA target genes that may serve as global markers of B[a]P-mediated genotoxic stress. The dysregulated miRNAs may provide valuable knowledge about potential transgenerational effects of sublethal exposure to chemicals

Therapeutic efficacy of chloroquine and sulfadoxine/pyrimethamine against Plasmodium falciparum infection in Somalia

Study on the therapeutic efficacy of treatments based on chloroquine and sulfadoxine/pyrimethamine in cases of malaria (Plasmodium falciparum) in Merka and Gabiley, Somalia.Daraasaad ku saabsan waxtarka ku daaweynta chloroquine iyo sulfadoxine/pyrimethamine cudurka duumada, degaannada soomaaliyeed ee Marka iyo Gabiley.Studio sull'efficacia terapeutica di trattamenti a base di clorochina e sulfadossina/pirimetamina nei casi di malaria (Plasmodium falciparum) a Merka e Gabiley, Somalia

Octyl Methoxycinnamate Modulates Gene Expression and Prevents Cyclobutane Pyrimidine Dimer Formation but not Oxidative DNA Damage in UV-Exposed Human Cell Lines

Octyl methoxycinnamate (OMC) is one of the most widely used sunscreen ingredients. To analyze biological effects of OMC, an in vitro approach was used implying ultraviolet (UV) exposure of two human cell lines, a primary skin fibroblast (GM00498) and a breast cancer (MCF-7) cell lines. End points include cell viability assessment, assay of cyclobutane pyrimidine dimers (CPDs) and oxidated DNA lesions using alkaline elution and lesion-specific enzymes, and gene expression analysis of a panel of 17 DNA damage–responsive genes. We observed that OMC provided protection against CPDs, and the degree of protection correlated with the OMC-mediated reduction in UV dose. No such protection was found with respect to oxidative DNA lesions. Upon UV exposure in the presence of OMC, the gene expression studies showed significant differential changes in some of the genes studied and the expression of p53 protein was also changed. For some genes, the change in expression seemed to be delayed in time by OMC. The experimental approach applied in this study, using a panel of 17 genes in an in vitro cellular system together with genotoxicity assays, may be useful in the initial screening of active ingredients in sunscreens

Assessment of genetically modified maize Bt11 x MIR162 x MIR604 x MON 89034 x 5307 x GA21 for food and feed uses, import and processing under Regulation (EC) No 1829/2003 (application EFSA-GMO-DE-2018-149)

Bt11 x MIR162 x MIR604 x MON 89034 x 5307 x GA21 was produced by conventional breeding of the GM maize events Bt11, MIR162, MIR604, MON 89034, 5307 and GA21. Accordingly, Bt11 x MIR162 x MIR604 x MON 89034 x 5307 x GA21 maize produces the transgenic proteins in the individual GM maize events (Cry1Ab, PAT, Vip3Aa20, PMI, mCry3A, MIR604 PMI, Cry1A.105, Cry2Ab2, eCry3.1Ab and mEPSPS). Event Bt11 maize expresses the insecticidal protein Cry1Ab that protects against feeding damage caused by certain lepidopteran pests and the phosphinothricin acetyltransferase (PAT) protein for weed control by providing tolerance to herbicide products containing glufosinate ammonium. Event MIR162 maize expresses the insecticidal protein Vip3Aa20 that protects against feeding damage caused by certain lepidopteran pests and the PMI protein which enables transformed plant cells to utilise mannose as a primary carbon source and therefore used as a selectable marker in the development of the MIR162 maize. Event MIR604 maize expresses the insecticidal protein mCry3A that protects against feeding damage caused by certain coleopteran pests and the MIR604 PMI protein which enables transformed plant cells to utilise mannose as a primary carbon source and therefore used as a selectable marker in the development of the MIR604 maize. Event MON 89034 maize expresses the insecticidal proteins Cry1A.105 and Cry2Ab2 that protect against feeding damage caused by certain lepidopteran pests. Event 5307 maize expresses the insecticidal protein eCry3.1Ab that protects against feeding damage caused by certain coleopteran pests and the PMI protein which enables transformed plant cells to utilise mannose as a primary carbon source and therefore used as a selectable marker in the development of the 5307 maize. Event GA21 expresses the double-mutated 5-enolpyruvylshikimate-3-phosphate synthase enzyme (mEPSPS) for weed control by providing tolerance to herbicide products containing glyphosate.The scientific documentation provided in the application for genetically modified maize Bt11 x MIR162 x MIR604 x MON 89034 x 5307 x GA21 is adequate for risk assessment, and in accordance with EFSA guidance on risk assessment of genetically modified plants for use in food or feed. The VKM GMO panel does not consider the introduced modifications in maize Bt11 x MIR162 x MIR604 x MON 89034 x 5307 x GA21 to imply potential specific health or environmental risks in Norway, compared to EU-countries The EFSA opinion is adequate also for Norwegian considerations. Therefore, a full risk assessment of maize Bt11 x MIR162 x MIR604 x MON 89034 x 5307 x GA21 was not performed by the VKM GMO Panel.Assessment of genetically modified maize Bt11 x MIR162 x MIR604 x MON 89034 x 5307 x GA21 for food and feed uses, import and processing under Regulation (EC) No 1829/2003 (application EFSA-GMO-DE-2018-149)publishedVersio

Molecular portrait of cisplatin induced response in human testis cancer cell lines based on gene expression profiles

<p>Abstract</p> <p>Background</p> <p>Testicular germ cell tumors (TGCTs) respond well to cisplatin-based chemotherapy and show a low incidence of acquired resistance compared to most somatic tumors. The reasons for these specific characteristics are not known in detail but seem to be multifactorial. We have studied gene expression profiles of testicular and colon cancer derived cell lines treated with cisplatin. The main goal of this study was to identify novel gene expression profiles with their functional categories and the biochemical pathways that are associated with TGCT cells' response to cisplatin.</p> <p>Results</p> <p>Genes that were differentially expressed between the TGCT cell lines vs the (somatic) HCT116 cell line, after cisplatin treatment, were identified using the significance analysis of microarrays (SAM) method. The response of TGCT cells was strikingly different from that of HCT116, and we identified 1794 genes that were differentially expressed. Functional classification of these genes showed that they participate in a variety of different and widely distributed functional categories and biochemical pathways. Database mining showed significant association of genes (n = 41) induced by cisplatin in our study, and genes previously reported to by expressed in differentiated TGCT cells. We identified 37 p53-responsive genes that were altered after cisplatin exposure. We also identified 40 target genes for two microRNAs, hsa-mir-372 and 373 that may interfere with p53 signaling in TGCTs. The tumor suppressor genes <it>NEO1 </it>and <it>LATS2</it>, and the estrogen receptor gene <it>ESR1</it>, all have binding sites for p53 and hsa-mir-372/373. <it>NEO1 </it>and <it>LATS2 </it>were down-regulated in TGCT cells following cisplatin exposure, while <it>ESR1 </it>was up-regulated in TGCT cells. Cisplatin-induced genes associated with terminal growth arrest through senescence were identified, indicating associations which were not previously described for TGCT cells.</p> <p>Conclusion</p> <p>By linking our gene expression data to publicly available databases and literature, we provide a global pattern of cisplatin induced cellular response that is specific for testicular cancer cell lines. We have identified cisplatin-responsive functional classes and pathways, such as the angiogenesis, Wnt, integrin, and cadherin signaling pathways. The identification of differentially expressed genes in this study may contribute to a better understanding of the unusual sensitivity of TGCT to some DNA-damaging agents.</p

Comparison of blood RNA isolation methods from samples stabilized in Tempus tubes and stored at a large human biobank

Additional file 3. Evaluation of reference gene stability. The non-normalized raw Cq-values of reference small ncRNAs for adult (n=12 Tempus tubes) and cord blood (n=3 Tempus tubes) samples collected in the Tempus tubes of the blood-RNA samples isolated using the three RNA isolation protocols

Risk assessment of methylsulfonylmethane (MSM). Opinion of the Norwegian Scientific Committee for Food and Environment

acceptedVersio

Risk assessment of melatonin. Opinion of the Norwegian Scientific Committee for Food and Environment

publishedVersio

Biomarkers of Human Exposure to Acrylamide and Relation to Polymorphisms in Metabolizing Genes

Acrylamide (AA) is formed in heat treated carbohydrate rich foods in the so-called Maillard reaction. AA is readily absorbed in the body and converted to glycidamide (GA) by epoxidation by the CYP2E1 (cytochrome P450 2E) enzyme. Both AA and GA may be detoxified through direct conjunction to glutathione by glutathione-S-transferases and GA by hydrolysis to glyceramide. Recently, we reported that biomarkers of AA exposure reflect intake of major food sources of AA; there were large interindividual variations in the blood ratio of GA-Hb/AA-Hb (GA- and AA-hemoglobin adducts). In this study we investigated whether the ratio of GA-Hb/AA-Hb in subjects could be related to polymorphic differences in genes coding for metabolizing enzymes CYP2E1, EPHX1 (microsomal epoxide hydrolase), GSTM1, GSTT1, and GSTP1, all being expected to be involved in the activation and detoxification of AA-associated adducts. We found significant associations between GSTM1 and GSTT1 genotypes and the ratio of GA-Hb/AA-Hb (p = 0.039 and p = 0.006, respectively). The ratio of GA-Hb/AA-Hb in individuals with the combined GSTM1- and GSTT1-null variants was significantly (p = 0.029) higher than those with the wild-type genotypes. Although the number of subjects was small, there were also significant associations with other combinations; CYP2E1 (Val179Val) plus GSTM1-null (p = 0.022); CYP2E1 (Val/Val), GSTM1-null plus GSTT1-null (p = 0.047); and CYP2E1 (Val/Val), GSTT1 null, EPHX1 (Tyr113Tyr) plus EPHX1 (His139Arg) (p = 0.018). Individuals with these combined genotypes had significantly higher blood ratio of GA-Hb/AA-Hb than other combinations. The observed associations correspond with what would be expected from the relative roles of these enzymes in activation and detoxification of AA, except for individuals with the EPHX1 (His139Arg) variant. The internal dose of genotoxic metabolite and also the concentration of AA in blood seem to be affected by these polymorphic genes. The genotypes and their combination may constitute useful biomarkers for the assessment of individual susceptibility to AA intake, and could add to the precision of epidemiological studies of dietary cancer

Protocol for risk assessment of “other substances”. The Norwegian Scientific Committee for Food and Environment

publishedVersio