Estrogen-like metabolites and DNA-adducts in urogenital schistosomiasis-associated bladder cancer. Issue 2 (10th April 2015)

• Record Type: Journal Article
• Authors: Gouveia, Maria João; Santos, Júlio; Brindley, Paul J.; Rinaldi, Gabriel; Lopes, Carlos; Santos, Lúcio L.; da Costa, José Manuel Correia; Vale, Nuno
• Is Part Of: Cancer letters. Volume 359:Issue 2(2015)
• Page Start: 226
• Page End: 232
• Publication Date: 2015-04-10
• Subjects: Squamous cell carcinoma -- Schistosomiasis -- Bladder -- Angola -- Catechol estrogen quinone -- DNA adduct; Cancer -- Periodicals; Neoplasms -- Periodicals; Cancer -- Périodiques; Electronic journals; 616.994
• DOI: 10.1016/j.canlet.2015.01.018
• Languages: English
• ISSNs: 0304-3835

Abstract

Highlights: An estrogen-DNA adduct may be involved in pathogenesis of the cell carcinoma of the bladder associated with S. haematobium. Metabolites can be expected to provide deeper understanding of the carcinogenesis UGS-induced bladder cancer. Biomarkers for diagnosis and/or prognosis of this neglected tropical disease-linked cancer. Abstract: An estrogen-DNA adduct mediated pathway may be involved in the pathogenesis of the squamous cell carcinoma of the bladder associated with infection with the blood fluke Schistosoma haematobium . Extracts from developmental stages of S. haematobium, including eggs, induce tumor-like phenotypes in cultured cells. In addition, estrogen-derived, reactive metabolites occur in this pathogen and in sera of infected persons. Liquid chromatography-mass spectrometry analysis was performed on urine from 40 Angolans diagnosed with urogenital schistosomiasis (UGS), half of who also presented UGS-associated squamous cell carcinoma and/or urothelial cell carcinoma. The analysis revealed numerous estrogen-like metabolites, including seven specifically identified in UGS cases, but not reported in the database of metabolites in urine of healthy humans. These schistosome infection-associated metabolites included catechol estrogen quinones (CEQ) and CEQ-DNA-adducts, two of which had been identified previously in S. haematobium . In addition, novel metabolites derived directly from 8-oxo-7, 8-dihydro-2′-deoxyguanosine (8-oxodG) were identified in urine of all 40 cases of UGS. These metabolites can be expected to provide deeper insights into the carcinogenesis UGS-induced bladder cancer, and as biomarkers for diagnosis and/or prognosis of this neglected tropical disease-linked cancer.