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Reduction of 8-oxod...
Reduction of 8-oxodGTP in the nucleotide pool by hMTH1 leads to reduction in mutations in the human lymphoblastoid cell line TK6 exposed to UVA
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- Fotouhi, Asal (författare)
- Stockholms universitet,Institutionen för genetik, mikrobiologi och toxikologi
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- Skiöld, Sara (författare)
- Stockholms universitet,Institutionen för genetik, mikrobiologi och toxikologi
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- Shakeri Manesh, Sara (författare)
- Stockholms universitet,Institutionen för genetik, mikrobiologi och toxikologi
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- Osterman-Golkar, Siv (författare)
- Stockholms universitet,Institutionen för genetik, mikrobiologi och toxikologi
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- Wojcik, Andrzej (författare)
- Stockholms universitet,Institutionen för genetik, mikrobiologi och toxikologi
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- Jenssen, Dag (författare)
- Stockholms universitet,Institutionen för genetik, mikrobiologi och toxikologi
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- Harms-Ringdahl, Mats (författare)
- Stockholms universitet,Institutionen för genetik, mikrobiologi och toxikologi
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- Haghdoost, Siamak (författare)
- Stockholms universitet,Institutionen för genetik, mikrobiologi och toxikologi
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(creator_code:org_t)
- Elsevier BV, 2011
- 2011
- Engelska.
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Ingår i: Mutation research. - : Elsevier BV. - 0027-5107 .- 1873-135X. ; 715:1-2, s. 13-18
- Relaterad länk:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- UVA has been suggested to play an important role in UV-induced mutagenesis. The mechanisms by which UVA induces mutations are still a matter of debate. Our aim was to investigate the protective capacity of hMTH1, a nucleotide pool sanitization enzyme with 8-oxodGTPase activity. Human B lymphoblastoid cells were stably transfected with shRNA directed against hMTH1. Clonogenic survival, mutations, intracellular and extracellular levels of 8-oxodG (8-oxo-7, 8-dihydro-2'-deoxyguanosine) and dG in the nucleotide pool of UVA-irradiated transfected and non-transfected cells were investigated. Mutations were determined in the thymidine kinase locus. Intracellular 8-oxodG and dG were measured using a modified ELISA and HPLC, respectively, after extraction of the nucleotide pool and conversion of nucleotides to their corresponding nucleosides. 8-oxodG in the medium was measured using ELISA. UVA-induced mutations were significantly higher while the survival was slightly lower in transfected compared to non-transfected cells. The increased mutation rate in transfected cells at increased exposure correlated with enhanced levels of 8-oxodG in the nucleotide pool, and a somewhat reduced level of 8-oxodG in the medium. The results indicate that the nucleotide pool is a significant target for UVA-induced mutations and implicates that hMTH1 plays an important role in protecting cells from UVA-induced oxidative stress.
Ämnesord
- NATURVETENSKAP -- Biologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences (hsv//eng)
Nyckelord
- Oxidative stress
- hMTH1
- Mutagenesis
- UVA
- 8-oxo-dG
- 8-OH-dG
- 8-oxo-dGTP
- Reactive oxygen species
- molekylärgenetik
- Molecular Genetics
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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