Aberrant repair of etheno–DNA adducts in leukocytes and colon tissue of colon cancer patients

Obtułowicz, Tomasz; Winczura, Alicja; Speina, Elżbieta; Swoboda, Maja; Janik, Justyna; Janowska, B.; Cieśla, Jarosław M.; Kowalczyk, Paweł; Jawień, Arkadiusz; Gackowski, Daniel

doi:10.1016/j.freeradbiomed.2010.06.027

Cited by 34 publications

(26 citation statements)

References 57 publications

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“…In the case of etheno adducts, this is possibly related to alkyladenine DNA glycosylase (Aag), the loss of which has been shown to increase etheno adduct levels in colon DNA (11). To illustrate the complexity of damage and repair in inflammation, several studies showed higher levels of etheno adducts in inflammatory conditions in mice and humans (10,11,52,53), whereas other reports noted lower levels of etheno adducts under pathological conditions (54,55). In peripheral blood lymphocytes of colorectal carcinoma patients, levels of etheno adducts as well as DNA repair rates were lower than in healthy subjects (54).…”

Section: )mentioning

confidence: 99%

Infection-induced colitis in mice causes dynamic and tissue-specific changes in stress response and DNA damage leading to colon cancer

Mangerich

Knutson

Parry³

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

216

294

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Helicobacter hepaticus -infected Rag 2 -/- mice emulate many aspects of human inflammatory bowel disease, including the development of colitis and colon cancer. To elucidate mechanisms of inflammation-induced carcinogenesis, we undertook a comprehensive analysis of histopathology, molecular damage, and gene expression changes during disease progression in these mice. Infected mice developed severe colitis and hepatitis by 10 wk post-infection, progressing into colon carcinoma by 20 wk post-infection, with pronounced pathology in the cecum and proximal colon marked by infiltration of neutrophils and macrophages. Transcriptional profiling revealed decreased expression of DNA repair and oxidative stress response genes in colon, but not in liver. Mass spectrometric analysis revealed higher levels of DNA and RNA damage products in liver compared to colon and infection-induced increases in 5-chlorocytosine in DNA and RNA and hypoxanthine in DNA. Paradoxically, infection was associated with decreased levels of DNA etheno adducts. Levels of nucleic acid damage from the same chemical class were strongly correlated in both liver and colon. The results support a model of inflammation-mediated carcinogenesis involving infiltration of phagocytes and generation of reactive species that cause local molecular damage leading to cell dysfunction, mutation, and cell death. There are strong correlations among histopathology, phagocyte infiltration, and damage chemistry that suggest a major role for neutrophils in inflammation-associated cancer progression. Further, paradoxical changes in nucleic acid damage were observed in tissue- and chemistry-specific patterns. The results also reveal features of cell stress response that point to microbial pathophysiology and mechanisms of cell senescence as important mechanistic links to cancer.

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Section: )mentioning

confidence: 99%

Infection-induced colitis in mice causes dynamic and tissue-specific changes in stress response and DNA damage leading to colon cancer

Mangerich

Knutson

Parry³

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

216

294

View full text Add to dashboard Cite

show abstract

“…Similarly, εA and εC repair rates were decreased in PBL of colorectal carcinoma (CRC) patients in comparison to healthy controls, suggesting that such decreased repair rate could be one of the risk factors for CRC development [99]. Indeed, inflammation and high fat diet are the major risk factors for CRC development.…”

Section: Repair Of Etheno-dna Adducts By Ber System and Human Cancersmentioning

confidence: 99%

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

Winczura

Zdzalik²,

Tudek

2012

Free Radical Research

Self Cite

109

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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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“…Corresponding non-cancerous and tumor DNA were prepared as previously described (12). For standardization purposes, the expression of β-actin of each specimen was quantified ( Table Ⅱ).…”

Section: Dna Extraction and Real-time Quantitative Pcr Analysismentioning

confidence: 99%

Correlation between increased copy number of mitochondrial DNA and clinicopathological stage in colorectal cancer

Yang¹

2011

Oncol Lett

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Abstract. Change of mitochondrial DNA (mtDNA) copy numbers is considered to be an important hallmark of cancers. However, whether quantitative changes in mtDNA occur during the initiation and progression of colorectal cancer remains to be determined. Quantitative change in mtDNA was observed during the initiation and progression of colorectal cancer and possible correlations of the mtDNA copy number in colorectal cancer with the clinicopathological stage were investigated. Tumor tissues and the corresponding noncancerous tissues were surgically resected from 24 colon and 20 rectal patients between 2008 and 2009. β-actin expression was quantified in all of the specimens, and the copy numbers were calculated. In colorectal cancer, the quantitative changes of mtDNA exhibited a significant increase. In 24 cases of colon cancer, the average relative mtDNA copy number ratios were 115.15±31.57 in cancer tissues and 54.09±13.22 in the corresponding non-cancerous tissues (p<0.01). Furthermore, in 20 cases of rectal cancer, the ratios were 145.6±43.83 in cancer tissues and 55.58±12.47 in the corresponding non-cancerous tissues (p<0.001). Following correlation with clinicopathological data, change of the mtDNA copy number in colorectal cancer exhibited a significant association with clinicopathological stage, but no association with gender. Moreover, this increase was particularly marked in stages Ⅰ and Ⅱ. Our results indicate that mtDNA copy number plays a significant role during the initiation and progression of colorectal cancer, particularly during early clinicopathological stages.

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Aberrant repair of etheno–DNA adducts in leukocytes and colon tissue of colon cancer patients

Cited by 34 publications

References 57 publications

Infection-induced colitis in mice causes dynamic and tissue-specific changes in stress response and DNA damage leading to colon cancer

Infection-induced colitis in mice causes dynamic and tissue-specific changes in stress response and DNA damage leading to colon cancer

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

Correlation between increased copy number of mitochondrial DNA and clinicopathological stage in colorectal cancer

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