DNA adducts in tumour, normal peripheral lung and bronchus, and peripheral blood lymphocytes from smoking and non-smoking lung cancer patients: correlations between tissues and detection by 32P-postlabelling and immunoassay

Györffy, Erika; Anna, Lívia; Győri, Zoltán; Segesdi, Judit; Minárovits, János; Soltész, Ibolya; Kostic, S; Csekeő, Attila; Poirier, Miriam C.; Schoket, Bernadette

doi:10.1093/carcin/bgh131

Cited by 46 publications

(34 citation statements)

References 34 publications

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“…54 Recently, it was shown that the DNA content of N7-methylguanine produced from N-nitroso compounds was higher in urinary bladder Schistosomal tumor tissues than in adjacent normal epithelium of Egyptian patients. 55 In contrast, previous findings 56 showed lower DNA adducts levels in tumor DNA when compared with DNA from adjacent normal tissue. 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.…”

Section: Discussionmentioning

confidence: 73%

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: 73%

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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“…Consistent with what we have previously reported (7,8), adduct levels were higher in nontumor cells compared with tumor cells. Several studies of other tissues that measured PAH-DNA adducts in both tumor and adjacent nontumor cells, including lung (38), laryngeal (39), pancreas (40), and liver (41), have also reported higher Research.…”

Section: Discussionmentioning

confidence: 98%

Polycyclic Aromatic Hydrocarbon–DNA Adducts in Prostate and Biochemical Recurrence after Prostatectomy

Rybicki

Neslund‐Dudas²,

Bock

et al. 2008

Clinical Cancer Research

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Purpose: DNA adduct levels may be influenced by metabolic activity, DNA repair capabilities, and genomic integrity, all of which play a role in cancer progression. Experimental Design: To determine if elevated DNA adducts are a marker for prostate cancer progression, we measured polycyclic aromatic hydrocarbon^DNA adducts by immunohistochemistry in prostate cells of 368 surgical prostate cancer patients treated at the Henry Ford Hospital in Detroit, Michigan, between September 1999 and July 2004. Patients were followed up to 5 years after surgery with relative risk for biochemical recurrence (BCR) estimated with a Cox proportional hazards model that adjusted for standard clinical risk factors. Results: At 1 year of follow-up, patients with adduct levels above the median in tumor cells [hazard ratio (HR), 2.40; 95% confidence interval (95% CI), 1.10-5.27] and nontumor cells (HR, 3.22; 95% CI, 1.40-7.39) had significant increased risk of BCR, but these HRs decreased to 1.12 (95% CI, 0.68-1.83) and 1.46 (95% CI, 0.89-2.41) in tumor and nontumor cells at 5 years postsurgery. When we restricted our analysis to patients with advanced-stage (III+) disease, those with high adduct levels in either tumor (53.5% versus 30.2%; P = 0.07) or nontumor (55.2% versus 28.6%; P = 0.02) cells had BCR rates almost 2-fold higher. In race-stratified analyses, the greatest risk of BCR associated with high adduct levels (in nontumor cells) was for African American patients younger than 60 years old (HR, 3.79; 95% CI, 1.01-14.30). Conclusions: High polycyclic aromatic hydrocarbon^DNA adduct levels in nontumor prostate cells are most strongly associated with BCR between 1 and 2 years after surgery and in patient subsets defined by younger age, advanced tumor stage, and African American race.

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“…Molecular epidemiology studies have shown that PAH-(B[a]P)-DNA adduct formation in the peripheral blood lymphocytes (PBL) is an index of exposure also of the target tissues (i.e., lung; refs. 4,5). Anti -B[a]PDE-DNA adduct detection in the accessible tissues (PBLs) has allowed us to show genotoxic exposure to PAHs in occupational (cokeries) and environmental (smoking, diet, and environmental) situations (6,7).…”

Section: Introductionmentioning

confidence: 99%

Micronuclei Related toAnti–B[a]PDE-DNA Adduct in Peripheral Blood Lymphocytes of Heavily Polycyclic Aromatic Hydrocarbon–Exposed Nonsmoking Coke-Oven Workers and Controls

Pavanello

Kapka

Siwinska

et al. 2008

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Micronuclei (MN) frequency associated to biologically effective dose of polycyclic aromatic hydrocarbons [PAH; anti-benzo[a]pyrene diolepoxide (B[a]PDE)-DNA] within the same subjects' peripheral blood lymphocytes (PBL) was evaluated. Study subjects were nonsmoking male Polish coke-oven workers (n = 49) and matched controls (n = 45) verified for PAH exposure by urinary 1-pyrenol. We found that coke-oven workers, heavily exposed to PAHs (80% workers exceeded the urinary 1-pyrenol biological exposure index value), presented significantly higher MN frequency in PBLs than controls (P < 0.01). Substantial difference was also found for adduct levels in PBLs (P < 0.01). Increase in MN levels was significantly related to anti -B[a]PDE-DNA formation, key adduct of the ultimate carcinogenic metabolite of B[a]P (n = 94; r = 0.47; P < 0.001). The dose-response relationship was improved when subjects with adduct levels above the 3rd tertile (z4.35 adducts/10 8 nucleotides) were excluded (n = 61; r = 0.69; P < 0.001). Saturation of adduct/MN formation at high levels may disturb the underlying relationship. Linear multiple regression analysis, without subjects of 3rd tertile adduct level (n = 61), revealed that adduct formation (t = 4.61; P < 0.001), but not 1-pyrenol, was the significant determinant in increasing MN. In conclusion, the increase in MN frequency is mainly related to the specific anti -B[a]PDE-DNA formation within PBLs of the same subject. Our results substantiate, with the use of an early indicator of biological effect as well, that workers are at higher cancer risk than controls. (Cancer Epidemiol Biomarkers Prev

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DNA adducts in tumour, normal peripheral lung and bronchus, and peripheral blood lymphocytes from smoking and non-smoking lung cancer patients: correlations between tissues and detection by 32P-postlabelling and immunoassay

Cited by 46 publications

References 34 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

Polycyclic Aromatic Hydrocarbon–DNA Adducts in Prostate and Biochemical Recurrence after Prostatectomy

Micronuclei Related toAnti–B[a]PDE-DNA Adduct in Peripheral Blood Lymphocytes of Heavily Polycyclic Aromatic Hydrocarbon–Exposed Nonsmoking Coke-Oven Workers and Controls

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