Effect of mammalian cell differentiation on response to exogenous 5-aminolevulinic acid

Effect of mammalian cell differentiation on response to exogenous 5-aminolevulinic acid
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DOI:
10.1111/j.1751-1097.1999.tb03279.x
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发表时间:
1999-02-01
影响因子:
3.3
通讯作者:
Kennedy, JC
Kennedy, JC
中科院分区:
生物学3区
文献类型:
--
作者:
Li, G;Szewczuk, MR;Kennedy, JC

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当在体内或体外暴露于外源性5-氨基乙酰丙酸(ALA)时,许多不同类型的哺乳动物细胞积累荧光和光敏浓度的原卟啉IX(PpIX)。大多数类型的恶性细胞比它们产生的正常细胞积累更多的ALA诱导的PpIX。大多数类型的恶性细胞也比它们的正常对应物分化更少。因此,我们认为恶性细胞表现出恶性ALA表型的可能性(当暴露于外源性ALA时,异常大量的PpIX积累)作为其低分化状态的直接结果,通过将人早幼粒细胞里尔HL-60和小鼠前脂肪细胞系3 T3 L1暴露于体外诱导剂,HL-60细胞在分化过程中积累较少的ALA诱导的PpIX,但3 T3 L1细胞积累较多。那么ALA表型的变化以及分化状态的变化似乎是细胞类型特异性的。ALA诱导的PpIX的积累减少,伴随着早幼粒细胞白血病细胞的分化,可能具有临床应用,用于快速定量的髓细胞白血病患者对分化治疗的反应。
Many different types of mammalian cells accumulate fluorescing and photosensitizing concentrations of protoporphyrin IX (PpIX) when exposed to exogenous 5-aminolevulinic acid (ALA) in vivo or in vitro. Most types of malignant cells accumulate substantially more ALA-induced PpIX than do the normal cells from which they arose. Most types of malignant cells also are less differentiated than their normal counterparts. We therefore considered the possibility that malignant cells demonstrate a malignant ALA phenotype (accumulate abnormally large amounts of PpIX when exposed to exogenous ALA) as a direct consequence of their less differentiated state, Human promyelocyte cell lille HL-60 and mouse preadipocyte cell line 3T3 L1 were induced to differentiate by exposing them to inducing agents in vitro, The HL-60 cells accumulated less ALA-induced PpIX when differentiated, but the 3T3 L1 cells accumulated more. It appears then that changes in the ALA phenotype with changes in the state of differentiation are cell type specific. The decreased accumulation of ALA-induced PpIX that accompanied differentiation of the promyelocytic leukemia cells may have clinical application for rapid quantitation of the response of myelocytic leukemia patients to differentiation therapy.