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Structure, expression and activation of fish ras genes
J M Rotchell1, J S Lee, J K Chipman
1Centre for Environmental Research, School of Chemistry, Physics and Environmental Science, University of Sussex, Falmer, Brighton BN1 9QJ, UK.
Aquatic Toxicology (Amsterdam, Netherlands)
|September 12, 2001
Summary
Ras gene mutations are linked to tumors in fish, but the specific mutations and their occurrence vary significantly by species. This species-specific pattern influences susceptibility to environmental contaminants and tumor development.
Area of Science:
- Environmental toxicology
- Molecular biology
- Oncology
Background:
- Ras genes are crucial for cell growth signaling and are frequently mutated in mammalian tumors, typically at specific codons.
- Fish ras genes share high sequence similarity with mammalian counterparts, suggesting a conserved role in cell signaling.
Purpose of the Study:
- To investigate the occurrence and patterns of ras gene mutations in fish exposed to genotoxic compounds and in feral fish from contaminated environments.
- To compare the ras mutational profiles in fish with those in mammalian and rodent models.
- To explore the species-specific susceptibility to environmentally induced tumors.
Main Methods:
- Experimental exposure of fish to genotoxic compounds to generate ras mutational profiles.
- Analysis of ras gene mutations in liver samples from feral fish collected from hydrocarbon-contaminated areas.
- Comparison of mutational spectra across different fish species, tissues, and exposure conditions.
Main Results:
- Experimental exposures revealed that the ras mutational spectrum in fish is influenced by the inducing compound, tissue, and species.
- A novel ras codon 16 mutation was identified in fish, differing from mammalian mutation sites.
- Ras gene mutations were detected in some feral fish species (tomcod, winter flounder, dragonet) from contaminated sites, but not in others (English sole, European flounder).
- The incidence and pattern of ras gene mutations in environmentally induced tumors were found to be species-specific.
Conclusions:
- Fish ras genes are involved in tumor formation, but their mutational profiles exhibit significant species-specific variations.
- These variations contribute to differences in susceptibility to environmental contaminants and tumor development observed in field and laboratory studies.
- Further research into the interaction of fish ras genes with other signaling pathway components and the role of promoting agents is needed to fully understand species susceptibility.