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Updated: Apr 22, 2026
Zebrafish as a Model to Assess the Teratogenic Potential of Nitrite
Published on: February 16, 2016
Histopathological lesions, P-glycoprotein and PCNA expression in zebrafish (Danio rerio) liver after a single
Sandrine P Machado1, Virgínia Cunha2, Maria Armanda Reis-Henriques1
1CIIMAR/CIMAR - Interdisciplinary Centre of Marine and Environmental Research, Laboratory of Environmental Toxicology, University of Porto, Rua dos Bragas, 289, 4050-123 Porto, Portugal.
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.
Insights
Zebrafish exposed to a carcinogen developed liver tumors and showed increased expression of P-glycoprotein (P-gp) and proliferating cell nuclear antigen (PCNA) proteins. This highlights zebrafish as a model for studying drug resistance and cancer mechanisms.
Area of Science:
- Environmental Toxicology
- Biochemistry
- Cancer Research
Background:
- Carcinogenic compounds in aquatic environments pose risks.
- ABC transporters and multidrug resistance (MDR) are known in mammals but less understood in fish.
- Zebrafish (Danio rerio) are a valuable model organism in biomedical research.
Purpose of the Study:
- To investigate the long-term effects of diethylnitrosamine (DEN) exposure on zebrafish liver.
- To evaluate the expression of P-glycoprotein (P-gp) and proliferating cell nuclear antigen (PCNA) proteins in DEN-induced hepatic tumors.
- To assess the role of zebrafish ABC transporters in disease mechanisms.
Main Methods:
- Zebrafish were exposed to diethylnitrosamine (DEN) to induce hepatic tumors.
- Histopathological analysis was performed at 6 and 9 months post-exposure.
- Protein expression levels of P-gp and PCNA were analyzed at 3, 6, and 9 months post-exposure.
Main Results:
- Hepatic histopathological alterations, including pre-neoplastic lesions, were observed in DEN-exposed zebrafish.
- P-glycoprotein (P-gp) and proliferating cell nuclear antigen (PCNA) protein expression were significantly up-regulated at 3, 6, and 9 months post-DEN exposure.
- DEN exposure successfully induced tumor formation and altered protein expression in zebrafish liver.
Conclusions:
- Zebrafish exhibit up-regulation of P-gp and PCNA in response to carcinogen-induced liver tumors.
- Zebrafish ABC transporters demonstrate functional similarities to mammalian systems in disease contexts.
- Zebrafish serve as a relevant biological model for investigating disease mechanisms, including cancer and drug resistance.
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