Genomic DNA analyses of spontaneous hepatocellular carcinomas in LEC rat liver using a new technique

An inbred rat strain, LEC (Long Evans Cinnamon) has been used as a model of human Wilson's disease. This animal suffers from a severe type of hepatiti s, the clinical manifestations of which are similar to human fulminant hepa titis for 4-5 months which is caused by accumulation of copper in the liver . The surviving rats develop chronic hepatitis, followed by the development of spontaneous hepatoma. In contrast to studies with hepatocellular carcin omas (HCCs), the studies have great advantages in that the animals have ide ntical genetic background, can be raised under a fixed condition, and the d evelopment of HCC is reproducible. We took two HCC samples and analysed the ir genomic DNA using RLGS (Restriction Landmark Genomic Scanning), which in volves two-dimensional electrophoresis of genomic DNA allowing the survey o f some 1,000 NotI sites throughout the genome. Using this technique, we dis covered landmark spots that were either decreased or increased in intensity in HCC and compared them with the RLGS profile obtained from the DNA of co ntrol normal LEC rat liver. Approximately 1,300 spots were compared, and th e intensity of two spots was found to be decreased about half and one was i ncreased 1.3-1.7 folds. Although the mechanism of these changes and the pro perties of the changed DNA are yet to be studied, recurrent genomic changes in the LEC rat HCC could prove to be a good model system for elucidating t he essential genetic events in association with hepatocarcinogenesis.