Tumour-like phenotypes in urothelial cells after exposure to antigens from eggs of Schistosoma haematobium: An oestrogen–DNA adducts mediated pathway?

• Published in: International journal for parasitology 2013-01, Vol.43 (1), p.17-26
• Main Authors: Botelho, Mónica C., Vale, Nuno, Gouveia, Maria João, Rinaldi, Gabriel, Santos, Julio, Santos, Lucio L., Gomes, Paula, Brindley, Paul J., Correia da Costa, José Manuel
• Format: Article
• Language: English
• Subjects: Animals; Antigens, Helminth - isolation & purification; Antigens, Helminth - metabolism; Antigens, Helminth - toxicity; Apoptosis; Biological and medical sciences; Bladder cancer; Cell Proliferation - drug effects; Comet Assay; Cricetinae; DNA Adducts - metabolism; DNA Adducts - toxicity; Eggs; Endothelial Cells - drug effects; Estrogens - metabolism; Estrogens - toxicity; Female; Fundamental and applied biological sciences. Psychology; Genotoxicity; Haematobia; HCV29 cells; Humans; LC-DAD/ESI-MS; Life cycle. Host-agent relationship. Pathogenesis; Male; Mass Spectrometry; Mesocricetus; Mutagens - isolation & purification; Mutagens - metabolism; Mutagens - toxicity; Oestrogen–DNA adducts; Oxidative Stress; Protozoa; Schistosoma haematobium; Schistosoma haematobium - pathogenicity; Trematoda; Urothelium - drug effects
• ISSN: 0020-7519; 1879-0135
• DOI: 10.1016/j.ijpara.2012.10.023

[Display omitted] ► The tumorigenic capacity of soluble egg antigens (SEA) of Schistosoma haematobium parasites was investigated. ► Schistosoma haematobium SEA increased the proliferation and decreased the apoptosis of urothelial cells in vitro. ► Schistosoma haematobium SEA increased oxidative stress and induced genotoxicity of urothelial cells in vitro. ► Mass spectrometry analysis identified catechol-oestrogens in S. haematobium SEA. ► An oestrogen–DNA adduct pathway to explain bladder carcinogenesis associated with S. haematobium infection is proposed. 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.