title: Estrogen-like metabolites and DNA-adducts in urogenital schistosomiasis-associated bladder 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.
authors.affiliation: Center for the Study of Animal Science, ICETA, University of Porto, Rua de D. Manuel II, Apt 55142, 4051-401 Porto, Portugal; Department of Infectious Diseases, R&D Unit, INSA-National Health Institute Dr. Ricardo Jorge, Rua de Alexandre Herculano 321, 4000-055 Porto, Portugal.
authors.forename: Maria João
authors.initials: MJ
authors.lastname: Gouveia
authors.affiliation: Center for the Study of Animal Science, ICETA, University of Porto, Rua de D. Manuel II, Apt 55142, 4051-401 Porto, Portugal; Clínica da Sagrada Esperança, Avenida Mortala Mohamed-Ilha de Luanda, Luanda, Angola; Experimental Pathology and Therapeutics Group, Research Center of Instituto Português de Oncologia, Rua Dr António B Almeida 4200-072 Porto, Portugal.
authors.forename: Júlio
authors.initials: J
authors.lastname: Santos
authors.affiliation: Department of Microbiology, Immunology & Tropical Medicine, and Research Center for Neglected Diseases of Poverty, School of Medicine & Health Sciences, George Washington University, Washington, DC 20037 USA.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Brindley
authors.affiliation: Department of Microbiology, Immunology & Tropical Medicine, and Research Center for Neglected Diseases of Poverty, School of Medicine & Health Sciences, George Washington University, Washington, DC 20037 USA.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Rinaldi
authors.affiliation: Experimental Pathology and Therapeutics Group, Research Center of Instituto Português de Oncologia, Rua Dr António B Almeida 4200-072 Porto, Portugal.
authors.forename: Carlos
authors.initials: C
authors.lastname: Lopes
authors.affiliation: Clínica da Sagrada Esperança, Avenida Mortala Mohamed-Ilha de Luanda, Luanda, Angola; Experimental Pathology and Therapeutics Group, Research Center of Instituto Português de Oncologia, Rua Dr António B Almeida 4200-072 Porto, Portugal.
authors.forename: Lúcio L
authors.initials: LL
authors.lastname: Santos
authors.affiliation: Center for the Study of Animal Science, ICETA, University of Porto, Rua de D. Manuel II, Apt 55142, 4051-401 Porto, Portugal; Department of Infectious Diseases, R&D Unit, INSA-National Health Institute Dr. Ricardo Jorge, Rua de Alexandre Herculano 321, 4000-055 Porto, Portugal. Electronic address: jose.costa@insa.min-saude.pt.
authors.forename: José Manuel Correia
authors.initials: JM
authors.lastname: da Costa
authors.affiliation: CIQ-UP, Chemistry and Biochemistry Department, Faculty of Sciences, University of Porto, Rua do Campo Alegre 687, 4169-007 Porto, Portugal. Electronic address: nuno.vale@fc.up.pt.
authors.forename: Nuno
authors.initials: N
authors.lastname: Vale
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D014408:Biomarkers, Tumor / Q000652:urine; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000469:parasitology / Q000652:urine*; D002648:Child; D018736:DNA Adducts / Q000652:urine*; D003839:Deoxyadenosines / Q000652:urine*; D004967:Estrogens / Q000652:urine*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D012548:Schistosoma haematobium / Q000502:physiology; D012553:Schistosomiasis haematobia / Q000150:complications / Q000235:genetics / Q000652:urine*; D001749:Urinary Bladder Neoplasms / Q000235:genetics / Q000469:parasitology / Q000652:urine*; D014551:Urinary Tract / Q000378:metabolism / Q000469:parasitology / Q000473:pathology; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D018736:DNA Adducts; D003839:Deoxyadenosines; D004967:Estrogens; C078251:2'-deoxy-7,8-dihydro-8-oxoadenosine
keywords: Angola; Bladder; Catechol estrogen quinone; DNA adduct; Schistosomiasis; Squamous cell carcinoma