同半胱胺酸，葉酸與甲硫胺酸對肝癌細胞HepG2生長與DNA傷害的影響

本研究以人類肝癌細胞HepG2為實驗模式，探討葉酸、甲硫胺酸與同半胱胺酸生化代謝互動性對人類肝癌HepG2細胞株生長與DNA傷害的影響。缺乏外源性甲硫胺酸之提供，即使補充高量葉酸也無法支持細胞生長。若添加同半胱胺酸硫化內酯（簡稱同半胱胺酸），隨著葉酸補充量增加，將同半胱胺酸代謝成甲硫胺酸，使細胞生長逐漸回復。在添加500μM同半胱胺酸與補充10μM葉酸（5倍高於培養液中葉酸正常量）後，使甲硫胺酸缺乏的HepG2細胞回復100%的相對生長率。然而當增加同半胱胺酸濃度至1000μM時，不管有無補充葉酸或甲硫胺酸，細胞生長的回復性卻受到抑制，其相對生長率比添加500μM同半胱胺酸的相對生長率降低。以瓊膠電泳法定性如細胞是否出現程式凋亡的DNA傷害，發現高量同半胱胺酸雖然抑制HepG2細胞生長，但並未造成細胞程式凋亡之DNA傷害。葉酸對此同半胱胺酸誘發之細胞毒性並無調節作用。由此可知，甲硫胺酸與葉酸代謝影響細胞清除同半胱胺酸能力，同時高量同半胱胺酸會導致抑制HepG2生長之細胞毒性。

關鍵字

葉酸；同半胱胺酸；甲硫胺酸；細胞生長； DNA傷害； HepG2細胞

並列摘要

The effects of homocysteine, folate and methionine metabolism on cellular growth and DNA damage were investigated in human hepatoma HepG2 cells. Methionine-deficient cells did not resume growth after receiving folate supplementation. In the presence of homocysteine thiolactone (homocysteine), the growth of methionine-deficient cells increased as folate supplementation increased, indicating that homocysteine was remethylated into methionine by folate supplements. At concentrations of 500 μM homocysteine and 10 μM folate, methionine-deficient cells recovered 100% relative growth rates. High levels of homocysteine (1000 μM) exerted cellular toxicity by suppressing cellular growth. The addition of methionine or folate can not modulate the suppressed growth induced by homocysteine. While cellular growth was inhibited, apoptotic DNA fragmentation was not evident in HepG2 cells treated with high concentrations of homocysteine in the presence or absence of folate supplements. Taken together, the results indicate that certain levels of homocysteine can be remethylated by folate supplements to provide endogenous methionine for the growth of methionine-deficient cells. However, high levels of homocysteine were toxic to human HepG2 cells.

並列關鍵字

folate ； homocysteine ； methionine ； growth ； DNA damage ； HepG2 cells

國際替代計量

同半胱胺酸，葉酸與甲硫胺酸對肝癌細胞HepG2生長與DNA傷害的影響

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