Long-chain adducts of trans-4-hydroxy-2-nonenal to DNA bases cause recombination, base substitutions and frameshift mutations in M13 phage☆

Kowalczyk, Paweł; Cieśla, Jarosław M.; Komisarski, Marek; Kuśmierek, Jarosław T.; Tudek, Barbara

doi:10.1016/j.mrfmmm.2004.01.007

Cited by 47 publications

(58 citation statements)

References 34 publications

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“…Chen and Chung [45] demonstrated that under oxidizing conditions the ratio of unsubstituted to substituted ethenoadenine is 6:100, of unsubstituted to substituted guanine equals 24:100, and the number of unsubstituted ethenoadducts is significantly decreased under nitrogen. However, our previous in vitro studies showed that in oxidizing conditions only guanosine yielded unsubstituted 1,N 2 -εdG, and only in the amount of 1-2 % of modified dG [39]. Unsubstituted ethenoadducts are formed from unsaturated fatty acids in animals and humans [47], however the exact pathway of their formation is not clear.…”

Section: Modification Of Dna Bases By Lpo Products and Their Processimentioning

confidence: 97%

“…dG and dC are primary targets, while dA reacts with much lower efficiency, and HNE adducts to dT are in minority [39]. Etheno-type adduct of HNE to guanosine, 1,N 2 ε-guanosine, and propano-type cyclic 1,N 2 -propanodeoxyguanine were shown to occur as four diastereoisomers of tetracyclic structure (purine condensed with ethano and furano rings) [40,41].…”

Section: Modification Of Dna Bases By Lpo Products and Their Processimentioning

confidence: 99%

“…Substituted LPO-derived cyclic DNA adducts, like HNE-DNA adducts strongly inhibit DNA synthesis by prokaryotic and eukaryotic DNA polymerases both in vitro and in cellular models [38,39]. In bacteria HNE increased the mutation rate in the lacZ gene of M13 phage transfected into wild type E. coli strain.…”

Section: Translesion Synthesis Of Exocyclic-dna Adducts and Their Mutmentioning

confidence: 99%

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Damage of DNA and proteins by major lipid peroxidation products in genome stability

Winczura

Zdzalik²,

Tudek

2012

Free Radical Research

Self Cite

107

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"Lipid peroxidation induced damage of DNA and proteins in genome stability" by Winczura et. al.We would like to thank the reviewers for their valuable comments. Enclosed, please find the revised version, which includes answers to all questions raised by the reviewers. We changed the text and table presentation according to reviewers recommendations. All changes are marked in the text in red.Sincerely yours

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Section: Modification Of Dna Bases By Lpo Products and Their Processimentioning

confidence: 97%

Section: Modification Of Dna Bases By Lpo Products and Their Processimentioning

confidence: 99%

Section: Translesion Synthesis Of Exocyclic-dna Adducts and Their Mutmentioning

confidence: 99%

See 1 more Smart Citation

Damage of DNA and proteins by major lipid peroxidation products in genome stability

Winczura

Zdzalik²,

Tudek

2012

Free Radical Research

Self Cite

107

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“…Moreover, 4-HNE induces intracellular production of ROS (9). This highly mutagenic aldehyde can also directly bind to DNA and induce clonal nuclear genome alterations (10).…”

mentioning

confidence: 99%

Hypoxia induces mitochondrial mutagenesis and dysfunction in inflammatory arthritis

Biniecka¹,

Fox²,

Gao³

et al. 2011

Arthritis & Rheumatism

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Objective. To assess the levels and spectrum of mitochondrial DNA (mtDNA) point mutations in synovial tissue from patients with inflammatory arthritis in relation to in vivo hypoxia and oxidative stress levels.Methods. Random Mutation Capture assay was used to quantitatively evaluate alterations of the synovial mitochondrial genome. In vivo tissue oxygen levels (tPO 2 ) were measured at arthroscopy using a Results. The median tPO 2 level in synovial tissue indicated significant hypoxia (25.47 mm Hg). Higher frequency of mtDNA mutations was associated with reduced in vivo oxygen tension (P ‫؍‬ 0.05) and with higher synovial 4-HNE cytoplasmic expression (P ‫؍‬ 0.04). Synovial expression of CytcO II correlated with in vivo tPO 2 levels (P ‫؍‬ 0.03), and levels were lower in patients with tPO 2 <20 mm Hg (P < 0.05). In vitro levels of mtDNA mutations, ROS, mitochondrial membrane potential, 8-oxo-dG, and 4-HNE were higher in synoviocytes exposed to 1% hypoxia (P < 0.05); all of these increased levels were rescued by SOD and DMOG and, with the exception of ROS, by NAC.Conclusion. These findings demonstrate that hypoxia-induced mitochondrial dysfunction drives mitochondrial genome mutagenesis, and antioxidants significantly rescue these events.

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“…HNE was negative in bacterial mutagenicity tests, however its epoxidized form has been tested positive (Chung et al, 1993). HNE was found to be responsible for recombination, base substitutions and frameshift mutations in M13 phage transfected in E.coli (Kowalczyk et al, 2004). Moreover it has been reported that 50 μM HNE treatment in human cells induces a high frequency of G.C to T.A mutations at the third base of codon 249 (AGG*) of the p53 gene (Hussain et al, 2000), a mutational hot spot in human cancers, particularly in hepatocellular carcinoma (Hsu et al, 1991).…”

Section: Mutagenicitymentioning

confidence: 96%

Lipid Peroxidation in Colorectal Carcinogenesis: Bad and Good News

Pizzimenti¹,

Toaldo²,

Pettazzoni³

et al. 2012

Colorectal Cancer Biology - From Genes to Tumor

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Long-chain adducts of trans-4-hydroxy-2-nonenal to DNA bases cause recombination, base substitutions and frameshift mutations in M13 phage☆

Cited by 47 publications

References 34 publications

Damage of DNA and proteins by major lipid peroxidation products in genome stability

Damage of DNA and proteins by major lipid peroxidation products in genome stability

Hypoxia induces mitochondrial mutagenesis and dysfunction in inflammatory arthritis

Lipid Peroxidation in Colorectal Carcinogenesis: Bad and Good News

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