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Formation and persistence of O6-(2-hydroxyethyl)-2′-deoxyguanosine in DNA of various rat tissues following a single dose of N-nitroso-N-(2-hydroxyethyl)urea. An immuno-slot-blot study


Ludeke, Barbara I; Kleihues, Paul (1988). Formation and persistence of O6-(2-hydroxyethyl)-2′-deoxyguanosine in DNA of various rat tissues following a single dose of N-nitroso-N-(2-hydroxyethyl)urea. An immuno-slot-blot study. Carcinogenesis, 9(1):147-151.

Abstract

Rabbit antibodies against O6-(2-hydroxyethyl)-2′-deoxyguanosine (O6-HEdG) were used to develop a highly sensitive immuno-slot-blot assay for this promutagenic base which enabled the quantitation of ≥ 3.6 μmol O6-HEdG/mol deoxy-guanosine, corresponding to ≥ 5 fmol in a 3-μg DNA sample. This assay was used to study DNA hydroxyethylation by N-nitroso-N-(2-hydroxyethyl)urea (HENU) in adult male F344 rats. Initial amounts of O6-HEdG 2 h after a single i.v. dose of 50 mg/kg were highest in kidney (81 μmol O6HEdG/mol deoxyguanosine), followed by lung and liver (67 and 55 μmol/mol dG respectively). Formation of O6-HEdG in cerebral DNA was considerably lower (18 μmol O6-HEdG/mol deoxyguanosine), probably reflecting delayed crossing of the blood—brain barrier by HENU due to its hydrophilicity. The formation of O6-HEdG in liver and kidney was strictly proportional to dose over a range of 5-50 mg HENU/kg. Repair of O6-HEdG was very rapid in liver (apparent half-life, 12 h), and somewhat slower in kidney and lung (approximate half-life, 40 h and 48 h respectively). In contrast, 62% of the initial amount of O6-HEdG in cerebral DNA was still present after 7 days. Saturation of the hepatic O6-alkyl-guanine-DNA alkyltransferase by pretreatment with N-nitrosodimethylamine (20 mg/kg) almost completely inhibited the removal of O6-HEdG, indicating that O6-HEdG is predominantly repaired by this repair enzyme

Abstract

Rabbit antibodies against O6-(2-hydroxyethyl)-2′-deoxyguanosine (O6-HEdG) were used to develop a highly sensitive immuno-slot-blot assay for this promutagenic base which enabled the quantitation of ≥ 3.6 μmol O6-HEdG/mol deoxy-guanosine, corresponding to ≥ 5 fmol in a 3-μg DNA sample. This assay was used to study DNA hydroxyethylation by N-nitroso-N-(2-hydroxyethyl)urea (HENU) in adult male F344 rats. Initial amounts of O6-HEdG 2 h after a single i.v. dose of 50 mg/kg were highest in kidney (81 μmol O6HEdG/mol deoxyguanosine), followed by lung and liver (67 and 55 μmol/mol dG respectively). Formation of O6-HEdG in cerebral DNA was considerably lower (18 μmol O6-HEdG/mol deoxyguanosine), probably reflecting delayed crossing of the blood—brain barrier by HENU due to its hydrophilicity. The formation of O6-HEdG in liver and kidney was strictly proportional to dose over a range of 5-50 mg HENU/kg. Repair of O6-HEdG was very rapid in liver (apparent half-life, 12 h), and somewhat slower in kidney and lung (approximate half-life, 40 h and 48 h respectively). In contrast, 62% of the initial amount of O6-HEdG in cerebral DNA was still present after 7 days. Saturation of the hepatic O6-alkyl-guanine-DNA alkyltransferase by pretreatment with N-nitrosodimethylamine (20 mg/kg) almost completely inhibited the removal of O6-HEdG, indicating that O6-HEdG is predominantly repaired by this repair enzyme

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Item Type:Journal Article, refereed, original work
Communities & Collections:National licences > 142-005
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:1 January 1988
Deposited On:16 Oct 2018 15:14
Last Modified:24 Nov 2018 02:54
Publisher:Oxford University Press
ISSN:0143-3334
OA Status:Green
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1093/carcin/9.1.147
Related URLs:https://www.swissbib.ch/Search/Results?lookfor=nationallicenceoxford101093carcin91147 (Library Catalogue)
PubMed ID:3275502

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