- 期刊
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補充葉酸對葉酸缺乏之人類肝癌HepG2細胞株的影響
Effect of Folate Supplementation on Folate-Deficient HepG2 Cell Line
摘要
本研究以人類肝癌細胞株HepG2為實驗模式，探討葉酸補充對葉酸缺乏的HepG2細胞之影響機制。根據本實驗室先前之研究結果，葉酸缺乏四週之HepG2細胞形態變異，生長停頓，DNA斷裂，及死亡率增加。補充甘胺酸，次黃嘌呤與胸腺嘧啶（葉酸生化代謝之產物）二週後使細胞生存率由45%升高至76%；若補充2μM葉酸，則使細胞生存率恢復至91%，顯示補充葉酸更能支持細胞生存。同時，補充2μM葉酸二週後也使葉酸缺乏細胞之形態變異恢復正常。細胞內空泡消失恢復密實形態。至於細胞之相對生長速率直至補充葉酸三週時才恢復70%。可能是完整之生化代謝協調之恢復需時較久。葉酸缺乏愈久之細胞，補充葉酸後回復正常時間愈長。五週葉酸缺乏之180-200 base pair的DNA斷裂片直至補充葉酸二週後仍然殘存，三週後才消失。細胞之形態變異在補充葉酸三週後仍尚未完全恢復正常。由此可知，補充2μM葉酸可預防缺乏葉酸四週所造成之細胞傷害加重惡化而導致死亡，也同時幫助受傷細胞恢復正常分子特性及生化代謝。若葉酸缺乏時間超過四週，則延遲補充葉酸恢復正常的時間。
並列摘要
Effects of folate supplementation on cellular morphology, viability, relative growth rates and DNA damage of human hepatoma HepG2 cells were investigated. Our previous studies have shown that HepG2 cells deficient in folate for 4 weeks exhibited morphological alteration, growth arrest, DNA fragmentation and decreased viability. In this present study, we found that cellular viability of 4-week folate-deficient HepG2 increased from 45% to 76% after supplementation of folate-mediated metabolites (glycine, hypoxanthine and thymidine: GHT) for 2 weeks. Supplementation of 2 μM folate alone for the same period of time increased cellular viability to 91%. It indicated that endogenous synthesis of GHT by folate-mediated metabolism can be better utilized than exogenous GHT for cellular survival. Morphological alteration of folate-deficient cells can also be normalized upon 2 week of folate supplementation, whereas cytosolic blebbing disappeared. However, the relative growth rates of folate-deficient HepG2 cells only recovered to 70% by 3 week of folate supplementation. DNA damage of 5-week of folate-deficient HepG2 cells was gradually repaired as 180-200 bp DNA fragment multimers disappeared upon folate supplementation for 3 weeks. Until then, cytosolic blebbling was reduced but cell morphology still remained abnormal. Our data suggested that 2μM folate could rescue folate-deficient HepG2 cells from cellular and genomic damage. As folate deficiency became more severe, the recovery from cellular damage required longer time.
延伸閱讀
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