Estrogen-like metabolites and DNA-adducts in urogenital schistosomiasis-associated bladder cancer

Maria João Gouveia, Júlio Santos, Paul J. Brindley, Gabriel Rinaldi, Carlos Lopes, Lúcio L. Santos, José Manuel Correia da Costa*, Nuno Vale

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

50 Citations (SciVal)

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.

Original languageEnglish
Pages (from-to)226-232
Number of pages7
JournalCancer Letters
Volume359
Issue number2
DOIs
Publication statusPublished - 10 Apr 2015
Externally publishedYes

Keywords

  • Angola
  • Bladder
  • Catechol estrogen quinone
  • DNA adduct
  • Schistosomiasis
  • Squamous cell carcinoma
  • Humans
  • Middle Aged
  • Male
  • Young Adult
  • Carcinoma, Squamous Cell/genetics
  • Aged, 80 and over
  • Adult
  • Female
  • Urinary Tract/metabolism
  • Child
  • Schistosomiasis haematobia/complications
  • Estrogens/urine
  • DNA Adducts/urine
  • Deoxyadenosines/urine
  • Animals
  • Urinary Bladder Neoplasms/genetics
  • Schistosoma haematobium/physiology
  • Adolescent
  • Aged
  • Biomarkers, Tumor/urine

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