title: Histopathological lesions, P-glycoprotein and PCNA expression in zebrafish (Danio rerio) liver after a single exposure to diethylnitrosamine.
abstract: The presence of carcinogenic compounds in the aquatic environment is a recognized problem. ABC transporters are well known players in the multidrug-resistance (MDR) phenomenon in mammals associated with resistance to chemotherapy, however little is known in fish species. Thus, the aim of this study was to induce hepatic tumours and evaluate long-term effects on P-glycoprotein (P-gp) and proliferating cell nuclear antigen (PCNA) proteins in Danio rerio liver, after exposure to diethylnitrosamine (DEN). Several hepatic histopathological alterations were observed in zebrafish after exposure to DEN including pre-neoplastic lesions 6 and 9 months post-exposure. After 3, 6 and 9 months of exposure to DEN, P-gp and PCNA proteins expression were up-regulated. In conclusion, this study has shown that zebrafish ABC transporters can play a similar role as in human disease, hence zebrafish can be used also as a biological model to investigate in more deep mechanisms involved in disease processes.
authors.affiliation: CIIMAR/CIMAR - Interdisciplinary Centre of Marine and Environmental Research, Laboratory of Environmental Toxicology, University of Porto, Rua dos Bragas, 289, 4050-123 Porto, Portugal.
authors.forename: Sandrine P
authors.initials: SP
authors.lastname: Machado
authors.affiliation: CIIMAR/CIMAR - Interdisciplinary Centre of Marine and Environmental Research, Laboratory of Environmental Toxicology, University of Porto, Rua dos Bragas, 289, 4050-123 Porto, Portugal; ICBAS/UP - Institute of Biomedical Sciences Abel Salazar, University of Porto, Largo Professor Abel Salazar, 2, 4099-003 Porto, Portugal.
authors.forename: Virgínia
authors.initials: V
authors.lastname: Cunha
authors.affiliation: CIIMAR/CIMAR - Interdisciplinary Centre of Marine and Environmental Research, Laboratory of Environmental Toxicology, University of Porto, Rua dos Bragas, 289, 4050-123 Porto, Portugal.
authors.forename: Maria Armanda
authors.initials: MA
authors.lastname: Reis-Henriques
authors.affiliation: CIIMAR/CIMAR - Interdisciplinary Centre of Marine and Environmental Research, Laboratory of Environmental Toxicology, University of Porto, Rua dos Bragas, 289, 4050-123 Porto, Portugal. Electronic address: mferreira@ciimar.up.pt.
authors.forename: Marta
authors.initials: M
authors.lastname: Ferreira
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000378:metabolism*; D000818:Animals; D002273:Carcinogens / Q000008:administration & dosage* / Q000494:pharmacology; D004052:Diethylnitrosamine / Q000008:administration & dosage* / Q000494:pharmacology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D008099:Liver / Q000378:metabolism / Q000473:pathology*; D008297:Male; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism*; D015027:Zebrafish
chemical_list: D018435:ATP Binding Cassette Transporter, Subfamily B; D002273:Carcinogens; D018809:Proliferating Cell Nuclear Antigen; D004052:Diethylnitrosamine
keywords: Hepatocarcinogens; Immunohistochemistry; P-gp; PCNA; Zebrafish