Fish p53 as a possible biomarker for genotoxins in the aquatic environment

The p53 gene is a tumour suppressor gene which has a fundamental role in ce ll cycle control and division, and in mammals certain genotoxic agents indu ce specific mutations in p53, leading to tumourigenesis. Fish have been inv estigated as models for studying carcinogens, but as yet very little data e xists that links exposure to specific chemicals with the aetiology of tumou rs found in wild populations. In this study, p53 was sequenced from five sp ecies of fish with a view to the possible use of mutations in the highly co nserved domains of p53 to identify genotoxins in the aquatic environment. A 0.8kb fragment of the cDNA encompassing the conserved DNA-binding domain o f p53 was sequenced in three Oncorhynchus salmonid fish: coho (O. kisutch), chum (O. keta), and chinook (O. tshawytscha) and full-length p53 cDNAs wer e sequenced in the puffer fish (Tetraodon miurus) and the barber (Barbus ba rbus). The full-length puffer fish and barber p53 cDNAs were 1834 bp and 17 90 bp in length, encoding a 367 aa protein and a 369 aa protein, respective ly. The deduced aa sequences of the p53 cDNA in the Oncorhynchus salmon sha red a 100% identity in the five conserved regions (I-V). Comparisons of the deduced aa sequences for puffer Fish and barbel p53 with other Fish p53s r evealed a high homology within the conserved DNA binding domain (68-86% for puffer fish and between 66-88% For barbel). "Conserved" domain I was not h ighly conserved in Fish, as it is in mammals, and, therefore, conserved dom ains Il-V ore most likely to provide the valuable sequences in fish p53 For use in mutational studies to fingerprint genotoxins in the aquatic environ ment. (C) 1999 Wiley-Liss, Inc.