Tsujiuchi T, Tsutsumi M, Kido A, Kobitsu K, Takahama M, Majima T, Denda A, Nakae D, Konishi Y
Department of Oncological Pathology, Cancer Center, Nara Medical University, Kashihara.
Jpn J Cancer Res. 1996 Nov;87(11):1111-5. doi: 10.1111/j.1349-7006.1996.tb03119.x.
Activation of telomerase has been reported in several human cancers, including 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 CDAA diet or a choline-supplemented L-amino acid-defined (CSAA) diet from 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 from 6-week-old rats. Telomerase activity was assessed by using a telomeric repeat amplification protocol (TRAP). Normal liver and background parenchyma of rats fed either of the diets for 10 weeks or 50 weeks showed weak telomerase activity. In contrast, markedly increased levels were demonstrated in hyperplastic nodules and HCCs. These results suggest that increased telomerase activity may be a biological feature of preneoplastic lesions that evolve to HCCs in rat liver.
据报道，端粒酶的激活存在于包括肝细胞癌（HCC）在内的多种人类癌症中。我们研究了在大鼠中由胆碱缺乏的L-氨基酸限定（CDAA）饮食诱导的肝癌发生过程中端粒酶的活性。雄性F344大鼠从6周龄开始接受CDAA饮食或补充胆碱的L-氨基酸限定（CSAA）饮食，为期75周，并在实验开始后的10周、50周和75周处死亚组大鼠。分别在喂食CDAA饮食50周和75周的大鼠中发现了增生性结节和HCC。正常对照肝脏标本取自6周龄大鼠。通过使用端粒重复序列扩增协议（TRAP）评估端粒酶活性。喂食两种饮食10周或50周的大鼠的正常肝脏和背景实质显示出较弱的端粒酶活性。相比之下，增生性结节和HCC中的端粒酶活性水平显著升高。这些结果表明，端粒酶活性增加可能是大鼠肝脏中发展为HCC的癌前病变的生物学特征。
