INCREASED TELOMERASE ACTIVITY IN HYPERPLASTIC NODULES AND HEPATOCELLULAR CARCINOMAS INDUCED BY A CHOLINE-DEFICIENT L-AMINO ACID-DEFINED DIET IN RATS

Activation of telomerase has been reported in several human cancers, i ncluding hepatocellular carcinomas (HCCs). We investigated telomerase activity during hepatocarcinogenesis induced by a choline-deficient L- amino acid-defined (CDAA) diet in rats. Male F344 rats were given a CD AA diet or a choline-supplemented L-amino acid-defined (CSAA) diet fro m 6 weeks of age for 75 weeks, and subgroups were killed 10 weeks, 50 weeks and 75 weeks after the beginning of the experiment. Hyperplastic nodules and HCCs were noted in rats fed a CDAA diet for 50 weeks and 75 weeks, respectively. Normal control liver specimens were obtained f rom 6-week-old rats. Telomerase activity was assessed by using a telom eric repeat amplification protocol (TRAP). Normal liver and background parenchyma of rats fed either of the diets for 10 weeks or 50 weeks s howed weak telomerase activity. In contrast, markedly increased levels were demonstrated in hyperplastic nodules and HCCs. These results sug gest that increased telomerase activity may be a biological feature of preneoplastic lesions that evolve to HCCs in rat liver.