PARENT SESSION
TA3 - The Japanese Medaka Model
Chair: Haasch, Mary1, 1 347 Faser Hall, University, MS, USA
Co-chair: Winn, Richard2, 2 2580 Devil's Ford Road, Whitehall Forest, WFSR, Athens, GA, USA
8:00 AM to 12:00 PM - Tuesday, 19 November 2002
Room Ballroom H
(351) Retinoblastoma (Rb) tumour suppressor gene mutations and tumourigenesis in medaka (Oryzias latipes): aquatic toxicology applications.
Rotchell, Jeanette*,1, Ostrander, Gary2, 1 University of Sussex, Brighton, East Sussex, United Kingdom2 Johns Hopkins University, Baltimore, Maryland, USA
ABSTRACT- Alterations in the retinoblastoma (Rb) gene have been correlated with a variety of human tumours including retinoblastoma and hepatocarcinoma. Despite representing only a fraction of all genes involved in carcinogenesis and other disease states, Rb has critical functions. It regulates normal cell cycle, maintaining genome integrity, and is vulnerable to toxic insult by the classes of contaminants prevalent in river and estuarine sediments. We previously isolated a medaka homolog of the human Rb gene with a predicted protein of 909 amino acids. DNA sequence analyses with other vertebrate Rb sequences demonstrates that the medaka Rb cDNA is highly conserved in regions of functional importance. In addition, single strand conformation polymorphism (SSCP) analysis has been used to screen chemically-induced retinoblastoma, hepatocarcinoma and adenoma tissues for mutations. Sequence evidence of significant alterations in the Rb cDNA sequence of chemically-induced hepatocarcinoma and retinoblastoma tissues will be presented. The results suggest that, in a controlled laboratory exposure, the molecular aetiology of the fish hepatocellular carcinoma and eye tumour models appear to involve Rb-implicated tumourigenesis. Conservation of the Rb gene in aquatic organisms will be discussed.
Key words: tumor suppressor gene, retinoblastoma, carcinogenesis, mutation