Bladder Tumor Contains Higher N7-Methylguanine Levels in DNA than Adjacent Normal Bladder Epithelium

Saad, Abeer A.; O’Connor, Peter J.; Mostafa, Mostafa H.; Metwalli, Nabila; Cooper, Donald P.; Margison, Geoffrey P.; Povey, Andrew C.

doi:10.1158/1055-9965.epi-05-0813

Cited by 35 publications

(25 citation statements)

References 33 publications

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“…The very clear differences indicate that the close correlation between the levels of DNA alkylation in normal and tumor tissue despite the very large difference in the levels of DNA damage might be partially correlated to the individual differences in modes of alkylating agent metabolism due to genetic polymorphism and/or DNA repair pathways. 55,57 Previous studies with urinary bladder 54 and other tissues 58,59 have indicated that higher levels of the DNA repair protein (i.e., O 6 -alkylguanine DNA alkyltransferase) may result in lower levels of O 6 -methylguanine in DNA. Therefore, the change towards a malignant phenotype could possibly be attributed in part to the differences in DNA repair levels.…”

Section: Discussionmentioning

confidence: 99%

Elevated oxidative stress and DNA damage and repair levels in urinary bladder carcinomas associated with schistosomiasis

Salim

Morimura

Menesi

et al. 2008

Intl Journal of Cancer

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To cast light on mechanisms underlying development of urothelial carcinomas (UCs) of the urinary bladder associated with Schistosomiasis, we immunohistochemically analyzed the relationship between oxidative stress markers, DNA single strand breaks (ssDNA) which could also measure the levels of base damage and apoptosis in DNA, and expression of DNA repair genes with levels of nitric oxide synthases in bladder carcinomas of Egyptian patients with or without Schistosoma hematobium infection. Marked elevation of 8-hydroxy-2 0 -deoxyguanosine (8-OHdG) levels was found in squamous cell carcinomas and UCs associated with Schistosomiasis when compared with non-Schistosomal carcinomas. This was accompanied by strong over expression of the DNA-repair genes, 8-oxoguanine-DNA-glycosylase and apurinic/ apyrimidinic endonuclease, as well as increased formation levels of ssDNA. Expression levels of inducible nitric oxide synthase (iNOS) which is known to be indirectly related to oxidative stress was higher in Schistosomal than in the non-Schistosomal carcinomas. However, expression of endothelial nitric oxide synthase was slightly stronger in non-Schistosomal than in the Schistosomal carcinomas. In conclusion, these findings suggest a strong correlation between Schistosoma haematobium infection and increased levels of oxidative stress accompanied by a continuous DNA damage and repair in UCs, all directly correlating with elevated iNOS. ' 2008 Wiley-Liss, Inc.Key words: oxidative stress; 8-OHdG; ROS; iNOS; eNOS; ssDNA; OGG1; APE-1; DNA repair; urinary bladder carcinoma; schistosomes Schistosomiasis (Bilharzia) is endemic in Egypt and also in other 75 countries worldwide, affecting more than 200 million people, and putting more than 1 billion population at great risk. 1 It has been well-documented that urinary bladder cancer is one of the major consequences of chronic infection with Schistosoma hematobium in many African and Middle East countries. 2 Among different species of Schistosoma inhibiting various countries and causing several diseases including cancers of the liver and colorectum, 3,4 the relationship between Schistosoma hematobium and urinary bladder cancer is the most important, and this organism has been classified by WHO/IARC as a Class 1 carcinogen. 5 When compared with their non-Schistosomal counterparts, Schistosoma-associated bladder carcinomas have 2 major clinicopathological features: the incidence reaches a peak in the 3rd-5th decades of life vs. the 7th decade in nonendemic areas, and there is significant increase in the ratios of squamous cell carcinomas (SCCs) to typical transitional urothelial carcinomas (UCs). 6 The SCCs associated with Schistosoma are extremely complex and heterogeneous, exhibiting a high level of resistance to radiotherapy and chemotherapy. However, they do not show distant metastasis in spite of their invasive characteristics and advanced clinical grades. Comparisons have already been made of SCCs and UCs of non-Schistosoma-related 7 and Schistosoma-associated origins, 8 but the fo...

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Section: Discussionmentioning

confidence: 99%

Elevated oxidative stress and DNA damage and repair levels in urinary bladder carcinomas associated with schistosomiasis

Salim

Morimura

Menesi

et al. 2008

Intl Journal of Cancer

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“…Some studies have found that the N 7 -MeG levels in bladder cancer patients are higher in the DNA from tumour tissue than in DNA from adjacent normal epithelium (Saad et al 2006). In 42 Egyptians with bladder cancer, using the 32 P-postlabelling technique, N 7 -MedG was detected in 93% of the DNA from the tumour and 74% of the normal bladder tissue sample.…”

Section: Environmental Carcinogen Biomarker Validation 523mentioning

confidence: 99%

Validation of biomarkers for the study of environmental carcinogens: a review

et al. 2008

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There is a need for validation of biomarkers. Our aim is to review published work on the validation of selected biomarkers: bulky DNA adducts, N-nitroso compounds, 1-hydroxypyrene, and oxidative damage to DNA. A systematic literature search in PubMed was performed. Information on the variability and reliability of the laboratory tests used for biomarkers measurements was collected. For the evaluation of the evidence on validation we referred to the ACCE criteria. Little is known about intraindividual variation of DNA adduct measurements, but measurements have a good repeatability irrespective of the technique used for their identification; reproducibility improved after the correction for a laboratory factor. A high-sensitivity method is available for the measurement of 1-hydroxypyrene in urine. There is consensus on validation of biomarkers of oxidative damage DNA based on the comet assay and chromatographic measurement in blood while urinary measurements by chromatographic assays are well validated, and ELISA-based assays appear to lack specificity. Immunoassays for the quantification of adducts of N-nitroso compounds are useful for large epidemiological studies, given their sensitivity, the small amount of DNA required and their potential for rapid and high-throughput analysis.

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“…During recent years, a considerable number of studies have supported the relationship between DNA adducts and cancer risk at various sites such as liver, lung, prostate, breast and bladder (Santella et al 2005, Bak et al 2006, Rybicki et al 2006, Saad et al 2006, Zhang et al 2006, Zhu et al 2006. Although, Kyrtopoulos (2006) in his recent review referred to the potential of DNA adducts as biomarkers of cancer risk, the progress achieved in terms of the identification of environmental or genetic factors which substantially affect cancer risk among the general population is still relatively limited.…”

Section: Resultsmentioning

confidence: 99%

Carcinogen DNA adducts and the risk of colon cancer: case–control study

et al. 2008

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Colorectal cancer represents 8.5% of all tumours at the King Faisal Specialist Hospital & Research Centre. Environmental and dietary carcinogens such as polycyclic aromatic hydrocarbons (PAHs) and heterocyclic amines (HCAs) have long been suspected to play a prominent role in colon cancer aetiology. We designed a caseÁcontrol study to test the hypothesis of whether or not the presence of DNA adducts can play a role in the aetiology of colon cancer. DNA adducts were measured in 24 cancerous and 20 non-cancerous tissue samples of newly diagnosed colon cancer patients by 32 P-post-labelling technique. Normal tissue from 19 hospital patients served as controls. The mean levels of adducts per 10 10 nucleotides in cancerous and non-cancerous tissue were 151.759217.27 and 114.819186.10, respectively; however, only adducts in cancerous tissue were significantly higher than controls (32.78957.51 per 10 10 nucleotides) with p-values of 0.017. No BPDE-DNA adducts were found. No relationship was found between urinary cotinine as a marker of tobacco smoke and 1-hydroxypyrene as an indicator of an individual's internal dose of PAHs and DNA adducts. In a logistic regression model, only adducts in cancerous tissue were associated with the subsequent risk of colon cancer, with an odds ratio of 3.587 (95% confidence interval 0.833Á15.448) after adjustment for age and the duration of living in the current region, but of a borderline significance (p 00.086). Although it is difficult to arrive at a definite conclusion from a small dataset, our preliminary results suggest the potential role of DNA adducts in the colon carcinogenesis process. Additional studies with larger sample sizes are needed to confirm our preliminary finding. It is also important to identify the structural characterization of these unknown DNA adducts in order to have a better understanding of whether or not environmental carcinogens play a role in the aetiology of colon cancer.

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Bladder Tumor Contains Higher N7-Methylguanine Levels in DNA than Adjacent Normal Bladder Epithelium

Cited by 35 publications

References 33 publications

Elevated oxidative stress and DNA damage and repair levels in urinary bladder carcinomas associated with schistosomiasis

Elevated oxidative stress and DNA damage and repair levels in urinary bladder carcinomas associated with schistosomiasis

Validation of biomarkers for the study of environmental carcinogens: a review

Carcinogen DNA adducts and the risk of colon cancer: case–control study

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