scholarly journals Guanine-specific DNA damage induced by γ-irradiated histone

2005 ◽  
Vol 388 (3) ◽  
pp. 813-818 ◽  
Author(s):  
Ayako FURUKAWA ◽  
Yusuke HIRAKU ◽  
Shinji OIKAWA ◽  
Catherine LUXFORD ◽  
Michael J. DAVIES ◽  
...  
Keyword(s):  
Dna Damage ◽  
Human Cancer ◽  
Histone H1 ◽  
Peroxyl Radicals ◽  
Sequence Specificity ◽  
Histone H2a ◽  
Γ Irradiation ◽  
Histone Protein ◽  
The Difference ◽  
High Yields

In γ-irradiation, •OH is directly generated from water and causes DNA damage leading to carcinogenesis. Exposure of proteins to γ-irradiation, in the presence of oxygen, gives high yields of hydroperoxides. To clarify whether these hydroperoxides, particularly those formed on DNA-binding histone proteins, participate in γ-irradiation-induced carcinogenesis, experiments using 32P-labelled DNA fragments obtained from human cancer-related genes were undertaken. Histone protein-hydroperoxides induced significant DNA damage in the presence of Cu(I). Histone H1- and H3-hydroperoxides showed stronger DNA damage compared with histone H2A- and H4-hydroperoxides at 0.7 μM. Histone H1-hydroperoxides caused Cu(I)-dependent DNA damage predominantly at guanine residues, especially at 5′-GGC-3′, 5′-GGA-3′, 5′-GGT-3′ and single G bases. In contrast, histone H3-hydroperoxides/Cu(I) induced DNA damage at 5′-G in GG sequences; this sequence specificity is identical with that generated by 2,2′-azobis (2-amidinopropane) dihydrochloride, which is known to produce peroxyl radicals (RO2•). The difference in site specificity of DNA damage induced by histone H1- and H3-hydroperoxides may arise from their amino acid composition or their mode of binding to DNA. The histone H1-hydroperoxides/Cu(I) system also induced 8-oxo-7,8-dihydro-2′-deoxyguanosine formation in calf thymus DNA. It is concluded that histone protein-hydroperoxides can induce guanine-specific DNA damage, which may contribute to γ-irradiation-induced carcinogenesis.

scholarly journals Mice lacking NF-κB1 exhibit marked DNA damage responses and more severe gastric pathology in response to intraperitoneal tamoxifen administration

2017 ◽  
Author(s):  
Michael D Burkitt ◽  
Jonathan M Williams ◽  
Tristan Townsend ◽  
Rachael Hough ◽  
Carrie A Duckworth ◽  
...  
Keyword(s):  
Dna Damage ◽  
Dna Damage Response ◽  
Cell Loss ◽  
Gastric Atrophy ◽  
Gastric Lesions ◽  
Γ Irradiation ◽  
Damage Response ◽  
Gastric Corpus ◽  
The Difference ◽  
Epithelial Lesions

AbstractBackgroundTamoxifen (TAM) has recently been shown to cause acute gastric atrophy and metaplasia in mice. We have previously demonstrated that the outcome of Helicobacter felis infection, which induces similar gastric lesions in mice, is altered by deletion of specific NF-κB subunits. Nfkb1-/- mice developed more severe gastric atrophy than wild-type (WT) mice 6 weeks after H. felis infection. In contrast, Nfkb2-/- mice were protected from this pathology. We therefore hypothesized that gastric lesions induced by TAM may be similarly regulated by signaling via NF-κB subunits.MethodsGroups of 5 female C57BL/6 (WT), Nfkb1-/-, Nfkb2-/- and c-Rel-/- mice were administered 150mg/kg TAM by IP injection. 72 hours later, gastric corpus tissues were taken for quantitative histological assessment. In addition, groups of 6 female WT and Nfkb1-/- mice were exposed to 12Gy γ-irradiation. Gastric epithelial apoptosis was quantified 6 and 48 hours after irradiation.ResultsTAM induced gastric epithelial lesions in all strains of mice, but this was more severe in Nfkb1-/- mice than WT mice. Nfkb1-/- mice exhibited more severe parietal cell loss than WT mice, had increased gastric epithelial expression of Ki67 and had an exaggerated gastric epithelial DNA damage response as quantified by γH2AX. To determine investigate whether the difference in gastric epithelial DNA damage response of Nfkb1-/- mice was unique to TAM induced DNA damage, or a generic consequence of DNA damage, we also assessed gastric epithelial apoptosis following γ-irradiation. 6 hours after γ-irradiation, gastric epithelial apoptosis was increased in the gastric corpus and antrum of Nfkb1-/- mice.ConclusionsNF-κB1 mediated signaling regulates the development of gastric mucosal pathology following TAM administration. This is associated with an exaggerated gastric epithelial DNA damage response. This aberrant response appears to reflect a more generic sensitization of the gastric mucosa of Nfkb1-/- mice to DNA damage.

Photolytic and thermal annealing of radical anions gamma-irradiated monocarboxylic acids

1979 ◽  
Vol 44 (12) ◽  
pp. 3632-3643 ◽  
Author(s):  
Karel Mach ◽  
Igor Janovský ◽  
Karel Vacek
Keyword(s):  
Thermal Annealing ◽  
Pivalic Acid ◽  
Esr Spectra ◽  
Paramagnetic Species ◽  
Radical Anions ◽  
Γ Irradiation ◽  
Before And After ◽  
Optical Bleaching ◽  
The Difference ◽  
Gamma Irradiated

Total yields of paramagnetic species, their optical bleaching and thermal annealing in acetic, propionic, a-butyric, isobutyric, and pivalic acid γ-irradiated at 77 K were followed by ESR spectroscopy. Radical anions, always found after irradiation, disappear during optical bleaching without formation of any paramagnetic product. During thermal annealing they are converted almost quantitatively into the α-radicals of the respective acid, with the exception of pivalic acid. Amounts of radical anions were estimated from the difference of integrated ESR spectra taken before and after optical bleaching. The results show that approximately equal amounts of the reduction and oxidation paramagnetic products of the γ-irradiation can be detected.

scholarly journals Withanolide D Enhances Radiosensitivity of Human Cancer Cells by Inhibiting DNA Damage Non-homologous End Joining Repair Pathway

2020 ◽  
Vol 9 ◽  
Author(s):  
Jerome Lacombe ◽  
Titouan Cretignier ◽  
Laetitia Meli ◽  
E. M. Kithsiri Wijeratne ◽  
Jean-Luc Veuthey ◽  
...  
Keyword(s):  
Dna Damage ◽  
Cancer Cells ◽  
Human Cancer ◽  
Repair Pathway ◽  
End Joining ◽  
Human Cancer Cells ◽  
Non Homologous End Joining

scholarly journals Monohydrazone Based G-Quadruplex Selective Ligands Induce DNA Damage and Genome Instability in Human Cancer Cells

2020 ◽  
Vol 63 (6) ◽  
pp. 3090-3103 ◽  
Author(s):  
Jussara Amato ◽  
Giulia Miglietta ◽  
Rita Morigi ◽  
Nunzia Iaccarino ◽  
Alessandra Locatelli ◽  
...  
Keyword(s):  
Dna Damage ◽  
Cancer Cells ◽  
Genome Instability ◽  
Human Cancer ◽  
Human Cancer Cells ◽  
G Quadruplex ◽  
Selective Ligands

scholarly journals Detection of repair activity during the DNA damage-induced G2 delay in human cancer cells

Oncogene ◽  
2001 ◽  
Vol 20 (27) ◽  
pp. 3486-3496 ◽  
Author(s):  
Gary D Kao ◽  
W Gillies McKenna ◽  
Tim J Yen
Keyword(s):  
Dna Damage ◽  
Cancer Cells ◽  
Human Cancer ◽  
Human Cancer Cells ◽  
Repair Activity ◽  
G2 Delay

Study of the biological effects and DNA damage exerted by a new dipalladium-Hmtpo complex on human cancer cells

2002 ◽  
Vol 90 (1-2) ◽  
pp. 51-60 ◽  
Author(s):  
Khalid Akdi ◽  
Rosario A. Vilaplana ◽  
Sanaa Kamah ◽  
Jorge A.R. Navarro ◽  
Juan M. Salas ◽  
...  
Keyword(s):  
Dna Damage ◽  
Cancer Cells ◽  
Human Cancer ◽  
Biological Effects ◽  
Human Cancer Cells

scholarly journals Does high-mobility-group non-histone protein HMG 1 interact specifically with histone H1 subfractions?

1979 ◽  
Vol 183 (3) ◽  
pp. 657-662 ◽  
Author(s):  
P D Cary ◽  
K V Shooter ◽  
G H Goodwin ◽  
E W Johns ◽  
J Y Olayemi ◽  
...  
Keyword(s):  
Specific Interaction ◽  
High Mobility ◽  
Histone H1 ◽  
High Mobility Group ◽  
Chromosomal Protein ◽  
Histone Protein ◽  
Total Histone ◽  
Equilibrium Sedimentation ◽  
Histone H5

The interaction of the non-histone chromosomal protein HMG (high-mobility group) 1 with histone H1 subfractions was investigated by equilibrium sedimentation and n.m.r. sectroscopy. In contrast with a previous report [Smerdon & Isenberg (1976) Biochemistry 15, 4242–4247], it was found, by using equilibrium-sedimentation analysis, that protein HMG 1 binds to all three histone H1 subfractions CTL1, CTL2, and CTL3, arguing against there being a specific interaction between protein HMG 1 and only two of the subfractions, CTL1 and CTL2. Raising the ionic strength of the solutions prevents binding of protein HMG 1 to total histone H1 and the three subfractions, suggesting that the binding in vitro is simply a non-specific ionic interaction between acidic regions of the non-histone protein and the basic regions of the histone. Protein HMG 1 binds to histone H5 also, supporting this view. The above conclusions are supported by n.m.r. studies of protein HMG 1/histone H1 subfraction mixtures. When the two proteins were mixed, there was little perturbation of the n.m.r. spectra and there was no evidence for specific interaction of protein HMG 1 with any of the subfractions. It therefore remains an open question as to whether protein HMG 1 and histone H1 are complexed together in chromatin.

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