PUBLICATION
Co-exposure to environmental carcinogens in vivo induces neoplasia-related hallmarks in low-genotoxicity events, even after removal of insult
- Authors
- Martins, M., Silva, A., Costa, M.H., Miguel, C., Costa, P.M.
- ID
- ZDB-PUB-180228-3
- Date
- 2018
- Source
- Scientific Reports 8: 3649 (Journal)
- Registered Authors
- Keywords
- none
- MeSH Terms
-
- Animals
- Carcinogens, Environmental/toxicity*
- DNA Damage/drug effects
- DNA Damage/genetics
- DNA Repair/drug effects
- DNA Repair/genetics
- Epoxide Hydrolases/genetics
- Glucuronosyltransferase/genetics
- Oxidative Stress/drug effects*
- Oxidative Stress/genetics
- Zebrafish/genetics*
- Zebrafish/metabolism*
- PubMed
- 29483554 Full text @ Sci. Rep.
Citation
Martins, M., Silva, A., Costa, M.H., Miguel, C., Costa, P.M. (2018) Co-exposure to environmental carcinogens in vivo induces neoplasia-related hallmarks in low-genotoxicity events, even after removal of insult. Scientific Reports. 8:3649.
Abstract
Addressing the risk of mixed carcinogens in vivo under environmentally-realistic scenarios is still a challenge. Searching for adequate biomarkers of exposure requires understanding molecular pathways and their connection with neoplasia-related benchmark pathologies. Subjecting the zebrafish model to realistic concentrations of two genotoxicants and carcinogens, cadmium and benzo[a]pyrene, isolated and combined, yielded low levels of DNA damage. Altogether, the organisms' mechanisms of DNA repair, oxidative stress and phases I and II were not overwhelmed after two weeks of treatment. Still, transcriptional responses related to detoxification (epoxide hydrolase and UDP-glucuronosyltransferase) were higher in animals subjected to the combination treatment, inclusively following depuration. Nonetheless, inflammation and formation of hyperplasic foci in fish epithelia were more severe in animals exposed to the combined substances, showing slower recovery during depuration. Additionally, the combination treatment yielded unexpected increased expression of a ras-family oncogene homologue after depuration, with evidence for increased tp53 counter-response in the same period. The findings indicate that oncogene expression, cell proliferation and inflammation, may not require noticeable DNA damage to occur. Furthermore, albeit absent proof for neoplasic growth, the removal of chemical insult may promote tissue recovery but does not entirely clear molecular and histopathological endpoints that are commonly associated to neoplasia.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping