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Intracellular deoxy...
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Golkar, Siv ÖstermanStockholms universitet,Institutionen för molekylär biovetenskap, Wenner-Grens institut
(författare)
Intracellular deoxyribonucleotide pool imbalance and DNA damage in cells treated with hydroxyurea, an inhibitor of ribonucleotide reductase
- Artikel/kapitelEngelska2013
Förlag, utgivningsår, omfång ...
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2013-09-27
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Oxford University Press (OUP),2013
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printrdacarrier
Nummerbeteckningar
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LIBRIS-ID:oai:DiVA.org:su-97032
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https://urn.kb.se/resolve?urn=urn:nbn:se:su:diva-97032URI
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https://doi.org/10.1093/mutage/get044DOI
Kompletterande språkuppgifter
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Språk:engelska
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Sammanfattning på:engelska
Ingår i deldatabas
Klassifikation
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Ämneskategori:ref swepub-contenttype
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Ämneskategori:art swepub-publicationtype
Anmärkningar
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AuthorCount:4;Funding agency:AstraZeneca 2094202, 2094204
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Imbalance in the nucleotide pool of mammalian cells has been shown to result in genotoxic damage. The goal of this study was to devise a sensitive, reproducible and simple method for detection of nucleotide pool changes in mammalian cells that could be used for problem-solving activities in drug development, e.g. mechanistic explanation of a positive response in a mammalian in vitro genotoxicity test. The method evaluated in this study is based on ethanol extraction of the total nucleotide pool, heat treatment and filtration, treatment with calf intestine alkaline phosphatase to convert nucleotides to nucleosides and analysis of the nucleosides by high-performance liquid chromatography with ultraviolet detection. The method was applied to measure the intracellular levels of deoxyribonucleotides in mouse lymphoma (ML) L5178Y cells treated with various concentrations of a model compound, hydroxyurea (HU), a ribonucleotide reductase inhibitor. DNA strand breakage and micronuclei formation were assessed in the same experiments. Imbalance of nucleotide pool (i.e. changes in the relative ratios between individual nucleotide pools) in HU-treated ML cells has been observed already at a concentration of 0.01 mmol/l, whereas genotoxic effects became apparent only at higher concentrations of HU (i.e. 0.25 mmol/l and higher) as indicated by formation of DNA strand breaks and micronuclei.
Ämnesord och genrebeteckningar
Biuppslag (personer, institutioner, konferenser, titlar ...)
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Czene, StefanStockholms universitet,Institutionen för molekylär biovetenskap, Wenner-Grens institut,AstraZeneca R&D, Safety Assessment, Dept Genet Toxicol, AstraZeneca, Södertälje, Sweden(Swepub:su)czene
(författare)
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Gokarakonda, AmulyaStockholms universitet,Institutionen för molekylär biovetenskap, Wenner-Grens institut
(författare)
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Haghdoost, SiamakStockholms universitet,Institutionen för molekylär biovetenskap, Wenner-Grens institut(Swepub:su)shagh
(författare)
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Stockholms universitetInstitutionen för molekylär biovetenskap, Wenner-Grens institut
(creator_code:org_t)
Sammanhörande titlar
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Ingår i:Mutagenesis: Oxford University Press (OUP)28:6, s. 653-6600267-83571464-3804
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