Washbrook R, Riley P A
Department of Molecular Pathology, UCL Medical School, London, UK.
Br J Cancer. 1997;75(10):1417-20. doi: 10.1038/bjc.1997.244.
This study was carried out to test the hypothesis that induction of intracellular porphyrin synthesis by delta-aminolaevulinic acid (ALA) used to sensitize cells in photodynamic therapy would be more efficient if the ALA was used in an esterified form. Contrary to expectation, the generation of tetrapyrroles (TP) by cultured epithelial cells (CNCM-I-221) exposed to equimolar concentrations (0.6 mM) of ALA or its methyl ester (ALA-ME) showed that the mean total TP production rate during 6 h incubation in serum-free medium was 0.13 fmol cell(-1) h(-1) for ALA-exposed cells compared with 0.04 fmol cell(-1) h(-1) for cells exposed to ALA-ME. Fluorescein diacetate uptake and conversion to fluorescein indicated intracellular non-specific esterase activity, implying that ALA-ME conversion to ALA can occur. Cells exposed to ALA-ME exhibited loss of a greater proportion of total tetrapyrroles in the form of extracellular protoporphyrin IX (PPIX; 22.8%) compared with 11.6% in ALA-treated cells with a corresponding reduction in cell-associated PPIX (P < 0.05). A variable initial elevation in haem levels in ALA-ME-treated cells was observed, but did not reach statistically significant levels.
在光动力疗法中用于使细胞致敏的δ-氨基乙酰丙酸（ALA）若以酯化形式使用，诱导细胞内卟啉合成的效率会更高。与预期相反，将培养的上皮细胞（CNCM-I-221）暴露于等摩尔浓度（0.6 mM）的ALA或其甲酯（ALA-ME）后，四吡咯（TP）的生成情况表明，在无血清培养基中孵育6小时期间，暴露于ALA的细胞的平均总TP生成率为0.13 fmol细胞⁻¹小时⁻¹，而暴露于ALA-ME的细胞为0.04 fmol细胞⁻¹小时⁻¹。二乙酸荧光素摄取并转化为荧光素表明细胞内存在非特异性酯酶活性，这意味着ALA-ME可以转化为ALA。与ALA处理的细胞中11.6%的比例相比，暴露于ALA-ME的细胞以细胞外原卟啉IX（PPIX；22.8%）的形式损失了更大比例的总四吡咯，同时细胞相关PPIX相应减少（P < 0.05）。观察到ALA-ME处理的细胞中血红素水平最初有可变升高，但未达到统计学显著水平。
