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

Fotouhi, Asal (författare): Stockholms universitet,Institutionen för genetik, mikrobiologi och toxikologi

Skiöld, Sara (författare): Stockholms universitet,Institutionen för genetik, mikrobiologi och toxikologi

Shakeri Manesh, Sara (författare): Stockholms universitet,Institutionen för genetik, mikrobiologi och toxikologi

Osterman-Golkar, Siv (författare): Stockholms universitet,Institutionen för genetik, mikrobiologi och toxikologi

Wojcik, Andrzej (författare): Stockholms universitet,Institutionen för genetik, mikrobiologi och toxikologi

Jenssen, Dag (författare): Stockholms universitet,Institutionen för genetik, mikrobiologi och toxikologi

Harms-Ringdahl, Mats (författare): Stockholms universitet,Institutionen för genetik, mikrobiologi och toxikologi

Haghdoost, Siamak (författare): Stockholms universitet,Institutionen för genetik, mikrobiologi och toxikologi

(creator_code:org_t)

Elsevier BV, 2011
2011
Engelska.
Ingår i: Mutation research. - : Elsevier BV. - 0027-5107 .- 1873-135X. ; 715:1-2, s. 13-18

Relaterad länk:: https://urn.kb.se/re...; visa fler...; https://doi.org/10.1...; visa färre...

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.

Av författaren/redakt...: Fotouhi, Asal; Skiöld, Sara; Shakeri Manesh, ...; Osterman-Golkar, ...; Wojcik, Andrzej; Jenssen, Dag; visa fler...; Harms-Ringdahl, ...; Haghdoost, Siama ...; visa färre...

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