Structure, expression and activation of fish ras genes

Ras genes encode proteins that play a central role in cell growth signaling cascades. The fish ras genes characterized to date, have a high degree of nucleotide sequence and deduced amino acid similarity with the mammalian ra s gene counterparts. A large proportion and wide variety of mammalian tumor s possess mutant forms of ras. In such cases, the localization of ras mutat ions has been restricted to exons I and II, and to codons 12, 13 and 61. Ex perimental exposure of fish to a range of genotoxic compounds has similarly led to the production of a ras mutational profile for selected species. Th e inducing compound, tissue investigated and the fish species studied affec t the ras mutational spectrum and incidence observed, despite the apparent conserved sequence homology. Furthermore, the fish ras mutational profile d iffers from that observed in rodent models, including a novel codon (16) mu tation. The role of ras genes in tumor formation in feral fish has been inv estigated using several species collected from areas of high hydrocarbon co ntamination. Tomcod (Microgadus tomcod), winter flounder (Pseudopleuronecte s americanus) and dragonet (Callionymus lyra) liver samples display evidenc e of ras gene mutations, though for the latter species the codon affected i s not characteristic of ras gene mutational profiles. English sole (Pleuron ectes vetulus) and European flounder (Platichthys flesus) liver tumor sampl es so far examined, on the other hand, do not display ras gene mutations. T hus, the pattern and incidence of ras gene mutations in environmentally-ind uced tumors also appear to be species specific. In determining the basis of both the species susceptibility observed in the field and species differen ces in effects of laboratory controlled exposures, the interaction of fish ras genes with other components of the cell growth signaling cascade (such as protein kinase C, additional oncogenes and tumor suppressor genes) are d iscussed. The effect of promoting agents following contaminant-induced init iation could similarly provide answers in unraveling the question of specie s susceptibility. ((C) 2001 Elsevier Science B.V. All rights reserved.