Promutagenic methylation damage in bladder DNA from patients with bladder cancer associated with schistosomiasis and from normal individuals

Badawi, Alaa; Mostafa, Mostafa H.; Aboul-Azm, T E; Haboubi, Najib; O’Connor, Peter J.; Cooper, Donald P.

doi:10.1093/carcin/13.5.877

Cited by 45 publications

(32 citation statements)

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“…Specific DNA adducts arising from exposure to aromatic amines such as benzidine, 4,4V-methylene-bis(2-chloroaniline), and 4-aminobiphenyl have also been detected in human bladder tissue or exfoliated bladder cells (16)(17)(18)(19). This study shows for the first time that DNA from bladder tumors and uninvolved normal tissue from the same patient contains detectable levels of N7-MedGp, indicating that bladder tissue is exposed to a methylating agent, confirming a previous report of the presence of O 6 -methylguanine in bladder DNA from cancer patients with schistosomiasis (20). DNA adduct levels in bladder DNA have been shown to vary considerably but tend to be of the order of tens or hundreds of adducts per 10 9 normal nucleotides, although higher levels have been reported (19), particularly if an individual has been accidentally exposed (17).…”

Section: Discussionsupporting

confidence: 87%

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

Saad

O’Connor²,

Mostafa³

et al. 2006

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Schistosoma haematobium -infected patients are more likely to develop bladder cancer and be more exposed to carcinogenic N-nitroso compounds than uninfected patients. As N7-methylguanine is a marker of exposure to methylating agents of this type, we have measured N7-methyldeoxyguanosine 3V-monophosphate (N7-MedGp) by 32 P postlabeling. DNA was isolated from 42 paired normal and tumor tissue of Egyptians with bladder cancer. N7-MedGp was detected in DNA from 93% of the tumors and 74% of the normal bladder tissue samples. Adduct levels were highly variable and ranged from 0.04 to 6.4 and from 0.02 to 0.72 Mmol/mol deoxyguanosine 3V-monophosphate (dGp) in tumor and normal DNA, respectively. N7-MedGp levels in normal and tumor DNA were highly correlated with one another (P = 0.007). The mean difference (95% confidence interval) in adduct levels between tumor and normal DNA was 0.21 (0.13-0.32) Mmol/mol dGp and this was statistically significant (P < 0.001). The adduct ratio (tumor DNA/normal DNA) varied between 0.2 and 136 (median, 4.6). N7-MedGp levels were not associated with gender, age, or the presence of schistosomiasis. However, lower N7-MedGp levels were found in normal DNA from individuals lacking the GSTM1 gene (P = 0.03) but not the GSTT1 gene or in subjects with the Ile105Val GSTP1 polymorphism. These results show that exposure to methylating agents is widespread and suggest that such exposure may play a role both in tumor initiation and progression. (Cancer Epidemiol Biomarkers Prev 2006; 15(4):740 -3)

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Section: Discussionsupporting

confidence: 87%

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

Saad

O’Connor²,

Mostafa³

et al. 2006

Cancer Epidemiology, Biomarkers &Amp; Prevention

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“…At values approaching the limit of detection, greater inter-assay variation was apparent, and this approached ± 35% as previously reported (Badawi et al, 1992). Assay variation has also been monitored by inclusion of a control sample which varied from 0.072 to 0.102 pmol of 06-MedG (0.086 ± 0.010, mean ± s.d.)…”

Section: -Methyldeoxyguanosine Analysissupporting

confidence: 68%

Formation and loss of O6-methyldeoxyguanosine in human leucocyte DNA following sequential DTIC and fotemustine chemotherapy

Lee

Margison²,

Thatcher³

et al. 1994

Br J Cancer

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There is increasing evidence to indicate that O6-methyldeoxyguanosine (O6-MedG) formation in DNA is a critical cytotoxic event following exposure to certain anti-tumour alkylating agents and that the DNA repair protein O6-alkylguanine-DNA alkyltransferase (ATase) can confer resistance to these agents. We recently demonstrated a wide inter-individual variation in the depletion and subsequent regeneration of ATase in human peripheral blood lymphocytes following sequential DTIC (400 mg m-2) and fotemustine (100 mg m-2) treatment, with the nadir ATase activity occurring approximately 4 h after DTIC administration. We have now measured the formation and loss of O6-methyldeoxyguanosine (O6-MedG) in the DNA of peripheral leucocytes of eight patients receiving this treatment regimen. O6-MedG could be detected within 1 h and maximal levels occurred approximately 3-5 h after DTIC administration. Following the first treatment cycle, considerable inter-individual variation was observed in the peak O6-MedG levels, with values ranging from 0.71 to 14.3 mumol of O6-MedG per mol of dG (6.41 +/- 5.53, mean +/- s.d.). Inter- and intra-individual variation in the extent of O6-MedG formation was also seen in patients receiving additional treatment cycles. This may be a consequence of inter-patient differences in the capacity for metabolism of DTIC to release a methylating intermediate and could be one of the determinants of clinical response. Both the pretreatment ATase levels and the extent of ATase depletion were inversely correlated with the amount of O6-MedG formed in leucocyte DNA when expressed either as peak levels (r = -0.59 and -0.75 respectively) or as the area under the concentration-time curve (r = -0.72 and -0.73 respectively). One complete and one partial clinical response were seen, and these occurred in the two patients with the highest O6-MedG levels in the peripheral leucocyte DNA, although the true significance of this observation has yet to be established.

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“…Ovarian carcinoma Ocular lymphoma High [7,[23][24][25][26][27][28][29] Low [30] Low [33] Mycobacterium tuberculosis Lung carcinoma Kaposi"s sarcoma Low [38][39][40][41][42][43] Low [44,45] Schistosoma species [54][55][59][60][61][62][63][64][65][66][67]73] Low [56,[74][75][76][77][78] Low [70] Low [80] Low [81][82] Tropheryma whippelii Lymphoma Gastric adenocarcinoma Low [108] Low [110] Liver flukes 1.Opisthorchis viverrini 2. Clonorchis sinensis…”

Section: Lung Carcinomamentioning

confidence: 99%

“…There is a large body of knowledge regarding the association between inflammation from schistosomal infections and squamous cell carcinoma of the bladder, especially in countries in Africa and the Middle East [54,55,[61][62][63][64][65]. In some countries with a high rate of schistosomal infections (such as Iraq, Malawi, Zambia, and Kuwait), bladder cancer was reported to be the leading malignant disease [59,66,67].…”

Section: Schistosoma Species and Cancer Developmentmentioning

confidence: 99%

Chronic bacterial and parasitic infections and cancer: a review

Samaras

Rafailidis

Mourtzoukou

et al. 2010

J Infect Dev Ctries

112

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Background: A relatively underestimated facet of infectious diseases is the association of chronic bacterial and parasitic infections with cancer development. Therefore, we sought to evaluate the evidence regarding the association of such infections with the development of malignancy, excluding the overwhelming evidence of the association of Helicobacter pylori and cancer. Methodology: We searched Pubmed, Cochrane, and Scopus without time limits for relevant articles. Results: There is evidence that some bacterial and parasitic infections are associated with cancer development. The level of evidence of this association varies from high to low; in any case, a long time interval is mandatory for the development of cancer. A high level of evidence exists for the association of Salmonella Typhi with gallbladder and hepatobiliary carcinoma; Opisthorchis viverrini and Clonorchis sinensis with cholangiocarcinoma; Schistosoma hematobium with bladder cancer; chronic osteomyelitis with squamous cell carcinoma of the skin; and hidradenitis suppurativa with squamous cell carcinoma of the skin. In contrast, the level of evidence regarding the association of Chlamydia spp. with cancer is low. Mycobacterium tuberculosis is associated with lung cancer, albeit probably not etiopathogenetically. Conclusions: A considerable number of bacterial infections and parasitic infections are associated with the development of cancer. Further research into recognizing additional associations of bacterial and parasitic infections with cancer is mandatory.

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Promutagenic methylation damage in bladder DNA from patients with bladder cancer associated with schistosomiasis and from normal individuals

Cited by 45 publications

References 0 publications

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

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

Formation and loss of O6-methyldeoxyguanosine in human leucocyte DNA following sequential DTIC and fotemustine chemotherapy

Chronic bacterial and parasitic infections and cancer: a review

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