title: Tumour-like phenotypes in urothelial cells after exposure to antigens from eggs of Schistosoma haematobium: an oestrogen-DNA adducts mediated pathway?
abstract: Chronic infection with the blood fluke, Schistosoma haematobium, is associated with squamous cell carcinoma of the bladder. Previously, it has been shown that soluble extracts of mixed sex adult S. haematobium worms (SWAP) are tumourigenic, both in vitro and in vivo. In addition, oestrogen-related molecules in SWAP of S. haematobium down-regulate oestrogen receptors (ERs) alpha and beta in oestrogen responsive cells. Moreover, schistosome oestrogens occur in sera of persons with schistosomiasis haematobia and repress transcription of ERs in urothelial cells. Given that eggs of S. haematobium are the developmental stage directly responsible for urogenital disease during schistosomiasis haematobia, we suspected that soluble antigens from S. haematobium eggs exhibit similar or more potent tumorigenic capacity. Here we investigated the tumorigenic potential of soluble egg antigens (Sh-SEA) of S. haematobium and the endocrine system in favouring parasitism by schistosomes. The findings confirmed that 6.25μg/ml of Sh-SEA was enough to stimulate cell proliferation, reduce apoptosis and increase oxidative stress of Sh-SEA-exposed urothelial cells. In addition, genotoxic effects of Sh-SEA on these cells were determined by using alkaline single-cell gel electrophoresis (Comet). Furthermore, Liquid Chromatography Diode Array Detection Electron Spray Ionisation Mass Spectrometry indicated the presence of catechol-oestrogens in S. haematobium SEA. A prospective oestrogen-DNA adduct mediated pathway in S. haematobium egg induced bladder cancer is also discussed.
authors.affiliation: Center for the Study of Animal Science, ICETA, University of Porto, Portugal. monicabotelho@hotmail.com
authors.forename: Mónica C
authors.initials: MC
authors.lastname: Botelho
authors.forename: Nuno
authors.initials: N
authors.lastname: Vale
authors.forename: Maria João
authors.initials: MJ
authors.lastname: Gouveia
authors.forename: Gabriel
authors.initials: G
authors.lastname: Rinaldi
authors.forename: Julio
authors.initials: J
authors.lastname: Santos
authors.forename: Lucio L
authors.initials: LL
authors.lastname: Santos
authors.forename: Paula
authors.initials: P
authors.lastname: Gomes
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Brindley
authors.forename: José Manuel
authors.initials: JM
authors.lastname: Correia da Costa
mesh_terms: D000818:Animals; D000947:Antigens, Helminth / Q000302:isolation & purification / Q000378:metabolism / Q000633:toxicity*; D017209:Apoptosis; D049109:Cell Proliferation / Q000187:drug effects; D020552:Comet Assay; D006224:Cricetinae; D018736:DNA Adducts / Q000378:metabolism / Q000633:toxicity*; D042783:Endothelial Cells / Q000187:drug effects*; D004967:Estrogens / Q000378:metabolism / Q000633:toxicity*; D005260:Female; D006801:Humans; D008297:Male; D013058:Mass Spectrometry; D008647:Mesocricetus; D009153:Mutagens / Q000302:isolation & purification / Q000378:metabolism / Q000633:toxicity*; D018384:Oxidative Stress; D012548:Schistosoma haematobium / Q000472:pathogenicity*; D019459:Urothelium / Q000187:drug effects*
chemical_list: D000947:Antigens, Helminth; D018736:DNA Adducts; D004967:Estrogens; D009153:Mutagens