Involvement of alkylating agents in schistosome-associated bladder cancer: the possible basic mechanisms of induction

Badawi, Alaa; Mostafa, Mostafa H.; O’Connor, Peter J.

doi:10.1016/0304-3835(92)90259-x

Cited by 30 publications

(17 citation statements)

References 91 publications

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“…In addition, two were AT -GC transitions which may arise through deamination of adenine to hypoxanthine: Chronic inflammation is associated with activation of macrophages which in turn produce high levels of nitric oxide, a known deaminating agent (30). Chronic inflammation of the urothel as a cause of malignant transformation is illustrated by schistosomiasis, a chronic parasitic disease known to be associated with an increased risk for bladder cancer in humans (31). The results of this study do not clarify the mechnism by which phenacetin induces urothelial carcinomas in man.…”

Section: P53 Mutations In Urothelial Cardnomascontrasting

confidence: 47%

p53 mutations in phenacetin-associated human urothelial carcinomas

Petersen¹,

Ohgaki²,

Lüdeke³

et al. 1993

Carcinogenesis

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Chronic abuse of the analgesic drug phenacetin is associated with an increased risk of development of transitional cell carcinomas of the urinary tract. It is unclear whether phenacetin acts through chronic tissue damage (phenacetin nephropathy) or via a genotoxic metabolite causing promutagenk DNA lesions. In the present study, we investigated 15 urothelial carcinomas from 13 patients with evidence of phenacetin abuse. Tumors were screened for p53 mutations in exons 5-8 by single-strand conformation polymorphism (SSCP) analysis, followed by direct sequencing of PCR-amplified DNA. p53 Mutations were detected in 8/14 primary tumors (57%). All except one were missense mutations located in exon 5 (three mutations), exon 6 (one), exon 7 (two) and exon 8 (one). The type of mutation varied, with a preference for CpG sites. A frameshift mutation resulting from the insertion of a single cytosine at codons 151/152 was detected in a bladder tumor and its lung metastasis. Urothelial carcinomas located in the renal pelvis and hi the ureter of the same patient exhibited two different mutations, strongly suggesting that they developed independently. Another patient had tumors in the renal pelvis and bladder, both of which contained the same p53 mutation, indicating intracavitary metastatic spread. This demonstrates that screening of p53 mutations allows the clonal origin of tumors in patients with multiple primary and metastatic lesions to be determined. None of the tumors investigated contained mutations in codons 12,13 or 61 of H-ras or K-ras protooncogenes.

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Section: P53 Mutations In Urothelial Cardnomascontrasting

confidence: 47%

p53 mutations in phenacetin-associated human urothelial carcinomas

Petersen¹,

Ohgaki²,

Lüdeke³

et al. 1993

Carcinogenesis

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“…This applies to both nonbilharzial 2,6,7,39-45 and bilharzial bladders. 1,10,14,37,[47][48][49][50][51][52] Table 1 shows the tumor (T) stage of bilharzial SCC of the bladder according to Egyptian reports 10,14,[48][49][50][51] in comparison to that of non-bilharzial SCC according to some western reports. 2,6,38,40,41,45 Another characteristic feature of bilharzial SCC is the degree of differentiation.…”

Section: Pathogenesismentioning

confidence: 99%

“…Prolonged exposure of these noninvasive transitional tumors to carcinogens can lead to development of the characteristic invasive SCC of the bilharzial bladder. 35 Many molecular biomarkers were recently studied to detect their impact on the clinical outcome after cystectomy for bilharzial bladder cancer. C-erbB-2 expression was detected in 33% of bilharzial SCCs.…”

Section: Pathogenesismentioning

confidence: 99%

Squamous cell carcinoma of the bilharzial and non-bilharzial urinary bladder: a review of etiological features, natural history, and management

El-Sebaie¹,

Zaghloul²,

Howard

et al. 2005

Int J Clin Oncol

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Squamous cell carcinoma of the urinary bladder, though uncommon in Europe and the United States, is the most common variety of bladder tumor in countries where urinary bilharziasis prevails. A great controversy still exists regarding its natural history and management. Here, we review the literature of bilharzial and nonbilharzial squamous cell carcinoma of the urinary bladder, focusing on large series. Our aim was to gather most of the published data about this disease entity, report it in a systematic comparative review, and attempt to identify the adverse features and variables behind its dismal outcome. The conclusions are that squamous cell carcinoma, whether bilharzial or nonbilharzial, has distinctive clinicopathological features, different from those of the transitional cell variety. These tumors usually present in advanced (muscle-invasive) stages. Pelvic nodal metastases are not common, and the incidence of distant metastases is less than that reported with transitional cell carcinoma. Local treatment, including cystectomy and adjunctive radiotherapy, is the most acceptable way of treating such tumors.

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“…Carcinoma of the urinary bladder is proposed which takes into account the interrelationships between different factors resulting from the infection, especially the role of alkylating agents that can contribute to the induction of this neoplasm (19). Gutierrez et al (20) was found that higher methylation index in schistosoma associated bladder cancer.…”

Section: Discussionmentioning

confidence: 99%

Methylguanine DNA Methyl Transferase Activities, Glutathione S Transferase and Nitric Oxide in Bladder Cancer Patients

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Dinçer

et al. 2006

Cancer Investigation

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Tumor formation is a multistep process that can be divided in to the stages of tumor initiation, promotion, and progression. DNA repair protein; MGMT is a key suicide enzyme that repairs the mispairing base methylguanine, which is induced in DNA as a minor lesion. The glutathione S transferases (GSTs) are a family of enzymes that are important to protect against alkylating agents. Nitric oxide, contributes to the regulation of tumor angiogenesis. A substantial body of experimental evidence supports the hypothesis that tumor angiogenesis is fundamental for the growth and metastasis of solid tumors. We measured the activities of GST, MGMT, and levels of NO3-/NO2- in the leukocytes from patients with bladder carcinoma and healthy controls and activities of MGMT in the tissue from patients with bladder carcinoma and adjacent normal tissue in bladder. Both GST and tissue MGMT activites were significantly increased in the patient group. There was no significant difference between controls and patients for MGMT activity in peripheral blood leukocytes (PBL). Nitrate/nitrite levels in PBL, there was no significant difference between controls and patients. Nitrate/nitrite levels were increased in G2-G3 tumors. In conclusion, we determined high concentrations of nitrite in leukocytes are suspected alkylation damage by induction nitrosamine. Increased DNA alkylation damage may lead the stimulation of MGMT and GST.

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Involvement of alkylating agents in schistosome-associated bladder cancer: the possible basic mechanisms of induction

Cited by 30 publications

References 91 publications

p53 mutations in phenacetin-associated human urothelial carcinomas

p53 mutations in phenacetin-associated human urothelial carcinomas

Squamous cell carcinoma of the bilharzial and non-bilharzial urinary bladder: a review of etiological features, natural history, and management

Methylguanine DNA Methyl Transferase Activities, Glutathione S Transferase and Nitric Oxide in Bladder Cancer Patients

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