Assessment of the genotoxic potential of ISIS 2302: a phosphorothioate oligodeoxynucleotide
| Autor: | Scott P, Henry, D K, Monteith, J E, Matson, B H, Mathison, K S, Loveday, R A, Winegar, P S, Lee, E S, Riccio, J P, Bakke, A A, Levin |
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| Rok vydání: | 2002 |
| Předmět: |
Male
Salmonella typhimurium Time Factors Health Toxicology and Mutagenesis Oligonucleotides Phosphorothioate Oligonucleotides CHO Cells Gene mutation Biology Toxicology medicine.disease_cause Chromosomes Oligodeoxyribonucleotides Antisense Mice In vivo Bone Marrow Cricetinae Genetics medicine Animals RNA Messenger Genetics (clinical) Chromosome Aberrations Dose-Response Relationship Drug Chinese hamster ovary cell Electrophoresis Capillary DNA Thionucleotides Molecular biology Immunohistochemistry In vitro medicine.anatomical_structure Models Chemical Mutation Female Bone marrow Micronucleus Genotoxicity Immunosuppressive Agents |
| Zdroj: | Mutagenesis. 17(3) |
| ISSN: | 0267-8357 |
| Popis: | ISIS 2302, a phosphorothioate oligodeoxynucleotide with antisense activity against human ICAM-1 mRNA, was evaluated in a battery of tests to assess genotoxic potential. There was no evidence of genotoxicity in three in vitro studies performed: (i) a bacterial reverse mutation test; (ii) a chromosomal aberration test in Chinese hamster ovary cells; (iii) a mammalian cell gene mutation assay in L5187Y cells. Additionally, there was no in vivo evidence of genetic toxicity in a bone marrow micronucleus study in male and female mice. For all tests, top concentrations or doses assessed met harmonized regulatory guidelines. The cellular uptake of ISIS 2302 into target cells was confirmed using capillary gel electrophoresis and immunohistochemistry. Intracellular uptake into CHO cells, L5187Y cells, Salmonella typhimurium TA98 and bone marrow was concentration- and time-dependent. Consistent with what is known about the physical and chemical properties of phosphorothioate oligodeoxynucleotides, there was no evidence of genotoxicity in any of the assessed end-points. Furthermore, the absence of genotoxicity could not be ascribed to test system insensitivity or to an absence of exposure of the test system to ISIS 2302. |
| Databáze: | OpenAIRE |
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