Maria Landin

• Yang, Yang; Pullisaar, Helen; Landin, Maria Augusta Dos S Silva; Heyward, Catherine Anne; Schröder, Maria; Geng, Tianxiang; Grano, Maria & Reseland, Janne Elin (2021). FNDC5/irisin is expressed and regulated differently in human periodontal ligament cells, dental pulp stem cells and osteoblasts. Archives of Oral Biology.  ISSN 0003-9969. . doi: https://doi.org/10.1016/j.archoralbio.2021.105061 Full text in Research Archive.
• Shabestari, Maziar; Ghadakchi Shabestari, Yashar; Landin, Maria Augusta Dos S Silva; Pepaj, Milaim; Cleland, Timothy; Reseland, Janne Elin & Eriksen, Erik Fink (2020). Altered protein levels in bone marrow lesions of hip osteoarthritis: Analysis by proteomics and multiplex immunoassays. International Journal of Rheumatic Diseases.  ISSN 1756-1841.  23(6), s 788- 799 . doi: 10.1111/1756-185X.13843 Full text in Research Archive.
• Shabestari, Maziar; Kise, Nina Jullum; Landin, Maria Augusta Dos S Silva; Sessing, Sølve; Hellund, Johan Castberg; Reseland, Janne Elin; Eriksen, Erik Fink & Haugen, Ida Kristin (2018). Enhanced angiogenesis and increased bone turnover characterize bone marrow lesions in osteoarthritis at the base of the thumb. Bone and Joint Research.  ISSN 2046-3758.  7(6), s 406- 413 . doi: 10.1302/2046-3758.76.BJR-2017-0083.R3 Full text in Research Archive.
• Kruger, Tormod Bjartveit; Herlofson, Bente Brokstad; Landin, Maria Augusta Dos S Silva & Reseland, Janne Elin (2016). Alendronate alters osteoblast activities. Acta Odontologica Scandinavica.  ISSN 0001-6357.  74(7), s 550- 557 . doi: 10.1080/00016357.2016.1217041
• Landin, Maria Augusta Dos S Silva; Nygård, Ståle; Shabestari, Maziar; Babaie, Eshrat; Reseland, Janne Elin & Osmundsen, Harald (2015). Mapping the global mRNA transcritome during development of the murine first molar. Frontiers in Genetics.  ISSN 1664-8021.  6(47) . doi: 10.3389/fgene.2015.00047 Full text in Research Archive. Show summary

  The main objective of this study was to map global geneexpression in order to provide information about the populations of mRNA species participating in murine tooth development at 24 h intervals, starting at the eleventh embryonic day (E11.5) up to the seventh post-natal day (P7). The levels of RNA species expressed during murine tooth development were mesured using a total of 58 deoxyoligonucleotide microarrays. Microarray data was validated using real-time RT-PCR. Differentially expressed genes (p<0.05) were subjected to bioinformatic analysis to identify cellular activities significantly associated with these genes. Using ANOVA the microarray data yielded 4362 genes as being differentially expressed from the elleventh embryonic day (E11.5) up to seven days post-natal (P7), 1921 of these being genes without known functions. The remaining 2441 genes were subjected to further statistical analysis using a supervised procedure. Bioinformatic analysis results for each time-point studied suggests that the main molecular functions associated with genes expressed at the early pre-natal stages (E12.5-E18.5) studied were cell cycle progression, cell morphology, lipid metabolism, cellular growth, proliferation, senescence and apoptosis, whereas most genes expressed at post-natal and secretory stages (P0- P7) were significantly associated with regulation of cell migration, biosynthesis, differentiation, oxidative stress, polarization and cell death. Differentially expressed genes (DE) not described earlier during tooth murine tooth development; Inositol 1, 4, 5-triphosphate receptor 3 (Itpr3), metallothionein 1(Mt1), cyclin-dependent kinase 4 (Cdk4), cathepsin D (Ctsd), keratin complex 2, basic, gene 6a (Krt2-6a), cofilin 1, non-muscle (Cfl1), cyclin 2 (Ccnd2), were verified by real-time quantitative RT-PCR and showed good agreement with results obtained from microarray.

• Sidaly, Rivan; Landin, Maria Augusta Dos S Silva; Suo, Zhenhe; Snead, Malcom; Lyngstadaas, Ståle Petter & Reseland, Janne Elin (2015). Hypoxia increases the expression of enamel genes and cytokines in an ameloblast-derived cell line. European Journal of Oral Sciences.  ISSN 0909-8836.  123(5), s 335- 340 . doi: 10.1111/eos.12201 Show summary

  The aim of the study was to investigate the effect of hypoxic conditions on the expression of enamel proteins, and secretion of alkaline phosphatase (ALP), cytokines and interleukins from an ameloblast-derived cell line. The murine ameloblast-derived cells (LS-8) were exposed to 1% oxygen concentration and harvested after 1, 2, 3 and 7 days. The effect of the hypoxic conditions for 24 and 48 h on gene expression, secretion of cytokines and interleukins, and alkaline phosphatase (ALP) activity into the cell medium was calculated relative to the expression and secretion from untreated cells (controls) at each timepoint. Hypoxic exposure increased the expression of the structural enamel matrix proteins; amelogenin (Amel), ameloblastin (Ambn), enamelin (Enam), and the enamel protease matrix metallopeptidase-20 (MMP-20). Expression of Hypoxia-inducible factor 1-alpha (Hif-1a) and secretion of several vascularization factors and pro-inflammatory factors were increased by 24 and 48 hours of hypoxia. ALP activity was reduced after 24 and 48 hours of hypoxia, whereas the LDH level in cell culture medium was higher after exposure to 24 hours compared to 48 hours of hypoxic conditions. In conclusion, hypoxic exposure may disrupt the controlled fine- tuned expression and processing of enamel proteins, and promote the secretion of pro-inflammatory factors.

• Pham, Thi Ngoc Maria Huong; Landin, Maria Augusta Dos S Silva; Tiainen, Hanna; Reseland, Janne Elin; Ellingsen, Jan Eirik & Haugen, Håvard Jostein (2014). The effect of hydrofluoric acid treatment of titanium and titanium dioxide surface on primary human osteoblasts. Clinical Oral Implants Research.  ISSN 0905-7161.  25(3), s 385- 394 . doi: 10.1111/clr.12150 Show summary

  Abstract Objective The aim of the study was to investigate solely the effect of fluoride on the surface chemistry of polycrystalline ceramic titanium dioxide (TiO2) and metallic titanium (Ti) and its effect on proliferation and differentiation of primary human osteoblasts (NHO). Materials and methods The NHO cells were exposed to fluoride-modified and unmodified samples for 1, 3, 7, 14 and 21 days. The fluoride effect on the mRNA expression was quantified and measured. The secretion of cytokines and interleukins in the cell culture medium was measured by Luminex, gene expression by RT-PCR, and compared with untreated controls. The effect on cell growth after 1 and 3 days in culture was measured using [3H]-thymidine incorporation. Fluoride release was measured using an ion-selective electrode. The surfaces were examined by X-ray photoelectron spectroscopy and profilometry. Results The fluoride release study detected that fluoride content easily washed off in TiO2 coins when compared with Ti coins. No increase in cell proliferation was found among fluoride-modified TiO2 surfaces compared with controls, except for washed Ti coins with fluoride modification. The cell differentiation with regard to gene expression showed no significant differences in both fluoride-modified and unmodified samples and less effect on protein release for all groups. Conclusions The fluoride from hydrofluoric acid treatment on Ti and TiO2 surfaces gave no specific effect on primary human osteoblast cells. The study indicates that the released fluoride is not the unique factor for the bioactivity of Ti and TiO2 surfaces.

• Riksen, Elisabeth Aurstad; Landin, Maria Augusta Dos S Silva; Reppe, Sjur; Nakamura, Yoikio; Lyngstadaas, Ståle Petter & Reseland, Janne Elin (2014). Enamel Matrix Derivative Promote Primary Human Pulp Cell Differentiation and Mineralization. International Journal of Molecular Sciences.  ISSN 1422-0067.  15(5), s 7731- 7749 . doi: 10.3390/ijms15057731 Full text in Research Archive.
• Pullisaar, Helen; Tiainen, Hanna; Landin, Maria Augusta Dos S Silva; Lyngstadaas, Ståle Petter; Haugen, Håvard Jostein; Reseland, Janne Elin & Østrup, Esben (2013). Enhanced in vitro osteoblast differentiation on TiO2 scaffold coated with alginate hydrogel containing simvastatin. Journal of Tissue Engineering.  ISSN 2041-7314.  4, s 1- 13 . doi: 10.1177/2041731413515670 Full text in Research Archive. Show summary

  The aim of this study was to develop a three-dimensional porous bone graft material as vehicle for simvastatin delivery and to investigate its effect on primary human osteoblasts from three donors. Highly porous titanium dioxide (TiO2) scaffolds were submerged into simvastatin containing alginate solution. Microstructure of scaffolds, visualized by scanning electron microscopy and micro-computed tomography, revealed an evenly distributed alginate layer covering the surface of TiO2 scaffold struts. Progressive and sustained simvastatin release was observed for up to 19 days. No cytotoxic effects on osteoblasts were observed by scaffolds with simvastatin when compared to scaffolds without simvastatin. Expression of osteoblast markers (collagen type I alpha 1, alkaline phosphatase, bone morphogenetic protein 2, osteoprotegerin, vascular endothelial growth factor A and osteocalcin) was quantified using real-time reverse transcriptase–polymerase chain reaction. Secretion of osteoprotegerin, vascular endothelial growth factor A and osteocalcin was analysed by multiplex immunoassay (Luminex). The relative expression and secretion of osteocalcin was significantly increased by cells cultured on scaffolds with 10 μM simvastatin when compared to scaffolds without simvastatin after 21 days. In addition, secretion of vascular endothelial growth factor A was significantly enhanced from cells cultured on scaffolds with both 10 nM and 10 μM simvastatin when compared to scaffolds without simvastatin at day 21. In conclusion, the results indicate that simvastatin-coated TiO2 scaffolds can support a sustained release of simvastatin and induce osteoblast differentiation. The combination of the physical properties of TiO2 scaffolds with the osteogenic effect of simvastatin may represent a new strategy for bone regeneration in defects where immediate load is wanted or unavailable.

• Kristoffersen, Anne Karin; Enersen, Morten; Kverndokk, Ellen Kristine; Sunde, Pia Titterud; Landin, Maria Augusta Dos S Silva; Solheim, Tore; Olsen, Ingar & Grinde, Bjørn (2012). Human papillomavirus subtypes in oral lesions compared to healthy oral mucosa. Journal of Clinical Virology.  ISSN 1386-6532.  53(4), s 364- 366 . doi: 10.1016/j.jcv.2011.12.023
• Landin, Maria Augusta Dos S Silva; Shabestari, Maziar Ghadakchi; Babaie, Eshrat; Reseland, Janne Elin & Osmundsen, Harald (2012). Gene expression profiling during murine tooth development. Frontiers in Genetics.  ISSN 1664-8021.  3 . doi: 10.3389/fgene.2012.00139 Show summary

  The aim of this study was to describe the expression of genes, including ameloblastin (Ambn), amelogenin X chromosome (Amelx), and enamelin (Enam) during early (pre-secretory) tooth development. The expression of these genes has predominantly been studied at post-secretory stages. Deoxyoligonucleotide microarrays were used to study gene expression during development of the murine first molar tooth germ at 24 h intervals, starting at the 11th embryonic day (E11.5), and up to the 7th day after birth (P7). The profile search function of Spotfire software was used to select genes with similar expression profile as the enamel genes (Ambn, Amelx, and Enam). Microarray results where validated using real-time reverse transcription-polymerase chain reaction (real-time RT-PCR), and translated proteins identified by Western-blotting. In situ localization of the Ambn, Amelx, and Enam mRNAs were monitored from E12.5 to E17.5 using deoxyoligonucleotide probes. Bioinformatics analysis was used to associate biological functions with differentially expressed (DE; p ≤ 0.05) genes. Microarray results showed a total of 4362 genes including Ambn, Amelx, and Enam to be significant DE throughout the time-course. The expression of the three enamel genes was low at pre-natal stages (E11.5–P0) increasing after birth (P1–P7). Profile search lead to isolation of 87 genes with significantly similar expression to the three enamel proteins. These mRNAs were expressed in dental epithelium and epithelium derived cells. Although expression of Ambn, Amelx, and Enam were lower during early tooth development compared to secretory stages enamel proteins were detectable by Western-blotting. Bioinformatic analysis associated the 87 genes with multiple biological functions. Around 35 genes were associated with 15 transcription factors.

• Qalb-E-Saleem, Khan Ahmed; Sehic, Amer; Skalleberg, Natalie Sharim; Landin, Maria Augusta Dos S Silva; Khuu, Cuong; Risnes, Steinar & Osmundsen, Harald (2012). Expression of delta-like 1 homologue and insulin-like growth factor 2 through epigenetic regulation of the genes during development of mouse molar. European Journal of Oral Sciences.  ISSN 0909-8836.  120(4), s 292- 302 . doi: 10.1111/j.1600-0722.2012.00976.x
• Qalb-E-Saleem, Khan Ahmed; Press, Charles McLean; Sehic, Amer; Landin, Maria Augusta Dos S Silva; Risnes, Steinar & Osmundsen, Harald (2010). Expression of prion gene and presence of prion protein during development of mouse molar tooth germ. European Journal of Oral Sciences.  ISSN 0909-8836.  118(6), s 559- 565 . doi: 10.1111/j.1600-0722.2010.00783.x
• Etokebe, Godfrey; Kuchler, Axel Matthias; Haraldsen, Guttorm; Landin, Maria Augusta Dos S Silva; Osmundsen, Harald & Dembic, Zlatko (2009). Family-with-sequence-similarity-46, member A (Fam46a) gene is expressed in developing tooth buds. Archives of Oral Biology.  ISSN 0003-9969.  54(11), s 1002- 1007 . doi: 10.1016/j.archoralbio.2009.08.005
• Lönn-Stensrud, Jessica; Landin, Maria Augusta Dos S Silva; Benneche, Tore; Petersen, Fernanda Cristina & Scheie, Anne Aamdal (2009). Furanones, potential agents for preventing Staphylococcus epidermidis biofilm infections?. Journal of Antimicrobial Chemotherapy.  ISSN 0305-7453.  63(2), s 309- 316 . doi: 10.1093/jac/dkn501
• Nilsen, Anja; Landin, Maria A.; Haug, Kristin Huse; Fonnum, Frode; Berger, Urs & Osmundsen, Harald (2008). Comparative hepatic gene expression profiling of rats treated with 1H, 1H, 2H, 2H-heptadecafluorodecan-1-o1 or with pentadecafluorooctanoic acid. Physiological Genomics.  ISSN 1094-8341.  34(3), s 285- 303 . doi: 10.1152/physiolgenomics.00225.2007
• Osmundsen, Harald; Landin, Maria Augusta Dos S Silva; From, Sigurd Hjalmar; Kolltveit, Kristin Melkevik & Risnes, Steinar (2007). Changes in gene-expression during development of the murine molar tooth germ. Archives of Oral Biology.  ISSN 0003-9969.  52, s 803- 813 . doi: 10.1016/j.archoralbio.2007.02.008 Full text in Research Archive. Show summary

  In a matter of a few days the murine tooth germ develops into a complex, mineralized, structure. Murine 30K microarrays were used to examine gene expression in the mandibular first molar tooth germs isolated at 15.5dpc and at 2DPN. Microarray results were validated using real-time RT-PCR. The results suggested that only 25 genes (3 without known functions) exhibited significantly higher expression at 15.5dpc compared to 2DPN. In contrast, almost 1400 genes exhibited significantly (P<0.015) higher expression at 2DPN compared to 15.5dpc, about half of which were genes with unknown functions. More than 50 of the 783 known genes exhibited higher than 10-fold increase in expression at 2DPN, amongst these were genes coding for enamel matrix proteins which were expressed several 100-fold higher at 2DPN. GO and KEGG analysis showed highly significant associations between families of the 783 known genes and cellular functions relating to energy metabolism, protein metabolism, regulation of cell division, cell growth and apoptosis. The use of bioinformatics analysis therefore yielded a functional profile in agreement with known differences in tissue morphology and cellular composition between these two stages. Such data is therefore useful in directing attention towards genes, or cellular activities, which likely are worthy of further studies as regards their involvement in odontogenesis

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• Gordeladze, Jan Oxholm; Landin, Maria Augusta Dos S Silva; Johnsen, Gaute Floer; Haugen, Håvard Jostein & Osmundsen, Harald (2017). Vitamin K2 and its Impact on Tooth Epigenetics. INTECH.  ISBN 978-953-51-3020-8.  27 s. Show summary

  The impact of nutritional signals plays an important role in systemic-based «models» of dental caries. Present hypotheses now focus both on the oral environment and other organs, like the nervous system and brain. The tooth is subjected to shear forces, nourishing and cleansing, and its present “support system” (the hypothalamus/parotid axis) relays endocrine signaling to the parotid gland. Sugar consumption enhances hypothalamic oxidative stress (ROS), reversing dentinal fluid flow, thus creating an enhanced vulnerability to the oral bacterial flora. The acid, produced by the oral bacterial flora, then leads to erosion of the dentine, and an irreversible loss of dental enamel layers. This attack brings about inflammatory responses, yielding metalloproteinase-based “dissolution”. However, vitamin K2 (i.e. MK-4/MK-7) may come to the rescue with its antioxidant property, locally (mouth cavity) or systemically (via the brain), thus sustaining/preserving hormone-induced dentinal fluid flow (encompassing oxidative stress) and boosting/magnifying bodily inflammatory responses. However, sugars may also reduce the tooth’s natural defences through endocrine signaling, thus enhancing acid-supported enamel dentine erosion. Vitamin K2 sustains and improves the salivary buffering capacity via its impact on the secretion/flow of calcium and inorganic phosphates. Interestingly, primitive cultures’ diets (low-sugar and high-K2 diets) preserve dental health.

• Osmundsen, Harald; Jevnaker, Anne-Marthe & Landin, Maria Augusta Dos S Silva (2012). kap 10 Deoxyoligonucleotide Microarrays for Gene Expression Profiling in Murine Tooth Germs. Springer.  ISBN 978-1-61779-860-3.  189 s. Show summary

  The use of deoxyoligonucleotide microarrays facilitates rapid expression profiling of gene expression using samples of about 1 μg of total RNA. Here are described practical aspects of the procedures involved, including essential reagents. Analysis of results is discussed from a practical, experimental, point of view together with software required to carry out the required statistical analysis to isolate populations of differentially expressed genes.

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• Landin, Maria Augusta Dos S Silva; Yashar Ghadakchi, Shabestari; Sehic, Amer; Reseland, Janne Elin & Osmundsen, Harald (2014). MK-7 enhances expression of genes related to bone, enamel and dentin, and reduces the expression of genes related to apoptosis in developing murine molars.
• Landin, Maria Augusta Dos S Silva; Lonn-Stensrud, Jessica; Petersen, Fernanda Cristina; Benneche, Tore & Scheie, Anne Aamdal (2013). Effekter av ikke toksiske furanoner på biofilm dannelse. Show summary

  Staphylococcus epidermidis (S. epidermis) er ofte påvist i biofilm som foråsaker infeksjoner forbundet med medisinske inplantater. Noen furanoner minsker biofilm dannelse tilsynelatende uten å forårsake irritasjon eller genotoksiske effekter, og uten å påvirke S. epidermidis vekst. Furanoner hindrer kommunikasjon mellom bakterier og har stor potensial for å hemme biofilm dannelse. Mål: Å studere biofilmhemmende og genotoksisk effekt av ulike furanoner Materialer og metoder: 11 furanoner ble undersøkt vha bioluminisens og biofilm assayer. MIC (minste inhiberende konsentrasjon) for disse furanonene ble bestemt for å undersøke om dannelse av biofilm eller bakterievekst ble påvirket. Effekter av furanoner på bakterie kommunikasjon ble også undersøkt ved bioluminisensmålinger. Preliminære genotoksiske effekter hos CD-1 muselever og nyrer ble undersøkt vha mikromatriser og membran matriser. Resultater: Fire furanoner ble valgt ut for videre biofilm analyser etter bioluminisens test. Hver furanon ble testet med konsentrasjoner som ikke påvirket bakterie proliferasjon, men biofilm dannelse ble signifikant redusert ved bruk av disse furanoner. For de to mest effektive furanoner (F202 og F202) som også ble testet in vivo, ble det ikke påvist akutt toksisitet eller genotoksisitet.

• Pham, Thi Ngoc Maria Huong; Landin, Maria Augusta Dos S Silva; Tiainen, Hanna; Reseland, Janne Elin; Ellingsen, Jan Eirik & Haugen, Håvard Jostein (2013). The Effect Of Hydrofluoric Acid Treatment Of Titanium And Titanium Dioxide Surface on Primary Human Osteoblasts.
• Pullisaar, Helen; Tiainen, Hanna; Landin, Maria Augusta Dos S Silva; Lyngstadaas, Ståle Petter; Haugen, Håvard Jostein; Reseland, Janne Elin & Østrup, Esben (2013). Coating titanium dioxide scaffold with simvastatin in alginate promote osteoblast differentiation in vitro.
• Pullisaar, Helen; Tiainen, Hanna; Landin, Maria Augusta Dos S Silva; Lyngstadaas, Ståle Petter; Haugen, Håvard Jostein; Reseland, Janne Elin & Østrup, Esben (2013). Enhanced in vitro bone differentiation on TiO₂ scaffold coated with simvastatin.
• Pullisaar, Helen; Tiainen, Hanna; Landin, Maria Augusta Dos S Silva; Lyngstadaas, Ståle Petter; Haugen, Håvard Jostein; Reseland, Janne Elin & Østrup, Esben (2013). Local delivery of simvastatin enhances bone differentiation on porous titanium dioxide scaffold.
• Pullisaar, Helen; Tiainen, Hanna; Landin, Maria Augusta Dos S Silva; Lyngstadaas, Ståle Petter; Haugen, Håvard Jostein; Reseland, Janne Elin & Østrup, Esben (2013). Local delivery of simvastatin on titanium dioxide scaffolds; a tissue engineering model.
• Landin, Maria Augusta Dos S Silva; Stunes, Astrid Kamilla; Syversen, Unni & Reseland, Janne Elin (2012). Adipokines expressed in cells participating in cranial development. Bone.  ISSN 8756-3282.  50, s S79- S79 . doi: 10.1016/j.bone.2012.02.230
• Landin, Maria Augusta Dos S Silva; Stunes, Kamilla; Osmundsen, Harald; Syversen, Unni & Reseland, Janne Elin (2012). Expression of adipokines during murine craniofacial and tooth development. Show summary

  Adipokines are pleiotropic secretory molecules thought mainly to be produced by adipose tissue. Leptin (LEP) is produced by adipocytes, osteoblasts, periodontal ligament cells (PDL) and chondrocytes. LEP acts on the central nervous system, in particular the hypothalamus, suppressing food intake and stimulating energy expenditure, as well as growth of various tissues including bone (1). Adiponectin (ADIPO) also known as anti-inflammatory adipokine appears to promote insulin sensitivity, fatty acid oxidation and mineral deposition in pulp cells (2). Resistin (RETN) is mainly associated with insulin resistance. Resistin has been shown to affect chemokines, cytokines and influence bone remodeling (3). Expression of these adipokines has not previously been identified in murine tooth germs, pulp cells or during craniofacial development

• Landin, Maria Augusta Dos S Silva & Osmundsen, Harald (2011). Mapping of gene expression during murine tooth development.
• Landin, Maria Augusta Dos S Silva (2010). Mapping of gene expression during murine tooth development : expression profiling of mRNAs in the developing murine first molar tooth germ.
• Landin, Maria Augusta Dos S Silva (2007). Mapping gene expression during tooth development an overview.
• Landin, Maria Augusta Dos S Silva (2007). Molecular biology methods in craniofacial development research.
• Landin, Maria Augusta Dos S Silva; Geronimo, Benedicto Abrigos; Woldene, Toril & Osmundsen, Harald (2007). Mapping gene expression during tooth development I.
• Landin, Maria Dos S Silva (2006). Differences in gene expression at various developmental stages of the murine molar tooth germ.
• Landin, Maria Dos S Silva (2006). Effekts of treatment of mice with hexabromocyclododecane (HBCD) on gene-expression in liver.
• Landin, Maria Dos S Silva (2006). Geneekspresjonsanalyser etter eksponering for HBCDD.
• Landin, Maria Dos S Silva (2005). Changes in gene-expression during development of the murine molar tooth-bud.
• Landin, Maria Dos S Silva (2005). Changes in gene-expression during development of the murine molar tooth-bud2.
• Landin, Maria Dos S Silva (2005). Effekter av bromerte flammehemmere på genekspresjon i muselever-en toksikogenomisk tilnærming. Toksikologen.  ISSN 1504-5773.  15(4), s 46- 47 . doi: www.nsft.net Show summary

  Toksikogenomikk forener metoder brukt i klassisk toksikologi og metoder fra molekylær biologi. Den nye disiplinen bruker transkripsjonal genprofilering som et ledd i risiko- vurdering for både nye og gamle kjemikaler som da kan testes for potensiell toksisitet på molekylærnivå. Dette gjøres ved å monitorere mRNA-nivået for mange tusen gener av gangen. Slik overvåking kan gi oss et bilde om hvordan kjemikalier eller andre forbindelser påvirker det molekylære maskineriet før synlige skader oppstår. Flammehemmere tilsettes produkter og materialer slik at risiko for antennelse og utvikling av brann reduseres betraktelig. HBCD og IBP er to av totalt 70 ulike bromerte organiske forbindelser. Disse brukes som flammehemmere. Toksikogenomiske metoder og teknikker ble brukt for å undersøke rapporten fra American Chemical Council CAS No.3194556 hvor industrien i USA utførte en risikovurdering for HBCD. Her kartlegges de biologiske effektene hos villtype og transgene mus etter eksponering for HBCD. Basert på denne undersøkelsen konkluderte American Chemical Council med at bruk av HBCD ikke utgjør noe miljørisiko. Total-RNA ble isolert fra lever og nyrer fra Balbc- og CD-1-villtypemus samt fra PPAR-alfa- knockoutmus. RNA konsentrasjon ble målt ved OD 260nm og med Ribogreen-metode. RNA-integritet ble bekreftet ved bruk av RT-PCR (revers-transkriptase). Deretter ble RNA amplifisert, merket og omgjort til cDNA. Dette ble hybridisert på membranmatriser eller mikromatriser for å kartlegge forandringer i genekspresjon. Resultatene fra membranmatrisene og fra mikromatrisene ble bekreftet med RT-PCR. Det ble kjørt enzymanalyser for katalase og acyl-CoA oksidase for å validere resultatene fra mikromatrisene. 1.1 Resultater fra HBCD eller IBP behandling: Kroppsvekt Behandling med HBCD eller IBP viste ikke endret kroppsvekt hos CD-1-villtype hannmus mens hunnmus viste betydelig tap av kroppsvekt. HBCD behandling førte til signifikant økning av kroppsvekt hos både PPAR-alfa knockout hunn- og hannmus. Levervekt Behandling med HBCD eller IBP viste forksjellige effekter på levervekt hos hann- og hunnmus både hos villtype og PPAR-alfa knockoutmus. Behandlingen førte til tap av levervekt både hos PPAR-alfa-knockout og villtype hunnmus mens hannmus viste signifikant økning av levervekt. Nyrevekt Behandling med HBCD eller IBP ga forskjellige effekter på nyrevekt hos PPAR-alfa knockout- og villtypemus. IBP ga reduksjon i nyrevekt både hos villtype og PPAR-alfa knockout hunnmus. HBCD-behandling førte til signifikant økning av nyrevekt hos PPAR-alfa knockoutmus. RT-PCR Behandling med HBCD eller IBP viste samme effekt på mRNA-mengde av utvalgte gener i muselever hos villtypemus. HBCD- eller IBP-behandlig førte til økning av mRNA- mengder for gener implisert i metabolisme av xenobiotika, tidlig respons med unntak av mRNA mendgder for oksidase og PPAR- alfa hvor behandling med 4 % HBCD førte til økte mRNA mengder mens 4 % IBP førte til signifikant reduksjon. Membranmatriser Behandling med HBCD og IBP ga forkjellige resultater for ekspresjon av gener (i muselever) implisert i varmestress (Hsp), oksidativt-stress, reparasjon av DNA og cellesyklus. Det samme gjelder for gener som koder for proteiner i ekstracellulær matriks (ECM). HBCD-behandling førte til suppresjon mens IBP førte til induksjon av disse genene. Behandling med HBCD eller IBP viste samme uttrykksmønstre på gener som uttrykkes ved inflammasjon og for gener som koder for vekstfaktorer, samt for gener som koder for adhesjonsmolekyler. Mikromatriser Hos villtypemus førte behandling med HBCD til induksjon av gener (i muselever) som kan påvirke apoptose, energi omsetning, oksidativt-stress, xenobiotika metabolisme og cellesyklus. Hos PPAR-alfa knockoutmus ble disse genene ikke tilstrekkelig indusert pga at PPAR-alfa-genet er slått av.

• Landin, Maria Dos S Silva (2004). Effects of treatment of PPAR-a knock-out mice with hexabromocyclododecane (HBCD).
• Landin, Maria Dos S Silva (2004). Effekter av Bromerte Flammehemere på Geneksprejon i Muselever. En toksikogenomisk tilnærming.
• Landin, Maria Augusta Dos S Silva (2004). Effekter av bromerte flammehemmere på genekspresjon i muselever : en toksikogenomisk tilnærming.

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