title: Investigation of micronucleus induction in MTH1 knockdown cells exposed to UVA, UVB or UVC.
abstract: The longer wave parts of UVR can increase the production of reactive oxygen species (ROS) which can oxidize nucleotides in the DNA or in the nucleotide pool leading to mutations. Oxidized bases in the DNA are repaired mainly by the DNA base excision repair system and incorporation of oxidized nucleotides into newly synthesized DNA can be prevented by the enzyme MTH1. Here we hypothesize that the formation of several oxidized base damages (from pool and DNA) in close proximity, would cause a high number of base excision repair events, leading to DNA double strand breaks (DSB) and therefore giving rise to cytogenetic damage. If this hypothesis is true, cells with low levels of MTH1 will show higher cytogenetic damage after the longer wave parts of UVR. We analyzed micronuclei induction (MN) as an endpoint for cytogenetic damage in the human lymphoblastoid cell line, TK6, with a normal and a reduced level of MTH1 exposed to UVR. The results indicate a higher level of micronuclei at all incubation times after exposure to the longer wave parts of UVR. There is no significant difference between wildtype and MTH1-knockdown TK6 cells, indicating that MTH1 has no protective role in UVR-induced cytogenetic damage. This indicates that DSBs induced by UV arise from damage forms by direct interaction of UV or ROS with the DNA rather than through oxidation of dNTP.
authors.affiliation: Center for Radiation Protection Research, Department of Molecular Biosciences, Wenner-Gren Institute, Stockholm University, Sweden.
authors.forename: Asal
authors.initials: A
authors.lastname: Fotouhi
authors.affiliation: Center for Radiation Protection Research, Department of Molecular Biosciences, Wenner-Gren Institute, Stockholm University, Sweden.
authors.forename: Nicola
authors.initials: N
authors.lastname: Cornella
authors.affiliation: Center for Radiation Protection Research, Department of Molecular Biosciences, Wenner-Gren Institute, Stockholm University, Sweden.
authors.forename: Mehrafarin
authors.initials: M
authors.lastname: Ramezani
authors.affiliation: Center for Radiation Protection Research, Department of Molecular Biosciences, Wenner-Gren Institute, Stockholm University, Sweden.
authors.forename: Andrzej
authors.initials: A
authors.lastname: Wojcik
authors.affiliation: Center for Radiation Protection Research, Department of Molecular Biosciences, Wenner-Gren Institute, Stockholm University, Sweden. Electronic address: Siamak.Haghdoost@su.se.
authors.forename: Siamak
authors.initials: S
authors.lastname: Haghdoost
mesh_terms: D002460:Cell Line; D053903:DNA Breaks, Double-Stranded; D004260:DNA Repair / Q000528:radiation effects; D045643:DNA Repair Enzymes / Q000235:genetics / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D006801:Humans; D048629:Micronuclei, Chromosome-Defective / Q000706:statistics & numerical data*; D015162:Micronucleus Tests; D018384:Oxidative Stress / Q000528:radiation effects; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics / Q000378:metabolism*; D014466:Ultraviolet Rays / Q000009:adverse effects* / Q000145:classification
chemical_list: D010744:Phosphoric Monoester Hydrolases; C078207:8-oxodGTPase; D045643:DNA Repair Enzymes
keywords: MTH1; Micronucleus; Oxidative stress; Reactive oxygen species; Ultraviolet radiation