TELOMERE LENGTH IN HUMAN LIVER-DISEASES

To determine the role of telomere-mediated gene stability in hepatocar cinogenesis, we examined the telomere length of human liver with or wi thout chronic liver diseases and hepatocellular carcinomas (HCC). The mean telomere restriction fragment (TRF) length of normal liver (n=13) , chronic hepatitis (n=11), liver cirrhosis (n=24) and HCC (n=24) was 7.8+/-0.2, 7.1+/-0.3, 6.4+/-0.2 and 5.2+/-0.2 kb, respectively (mean+/ -standard error). TRF length decreased with a progression of chronic l iver diseases and that in HCC was significantly shorter than that in o ther chronic liver diseases (p<0.05). The ratios of TRF length of HCC to that of corresponding surrounding liver of well differentiated (n=7 ), moderately differentiated (n=10) and poorly differentiated (n=4) HC Cs were 0.83+/-0.06, 0.75+/-0.05 and 0.98+/-0.09, respectively The rat io of poorly differentiated HCC was significantly higher than that of moderately differentiated HCC (p<0.05). A comparison between the size and telomere length ratio of moderately differentiated HCCs revealed a decrease of the ratio with size until it reached 50 mm in diameter. I n contrast, the ratio increased as the size enlarged over 50 mm. These findings suggest that the gene stability of the liver cells mediated by the telomere is reduced as chronic liver disease progresses and tha t telomerase is activated in poorly differentiated HCC and moderately differentiated HCC over 50 mm in diameter.