SELECTIVE ACCUMULATION OF ENDOGENOUSLY PRODUCED PORPHYRINS IN A LIVER METASTASIS MODEL IN RATS
SELECTIVE ACCUMULATION OF ENDOGENOUSLY PRODUCED PORPHYRINS IN A LIVER METASTASIS MODEL IN RATS
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DOI：
10.1016/0016-5085(92)90860-2
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发表时间：
1992-08-01
期刊：
影响因子：
29.4
通讯作者：
WILSON, JHP
中科院分区：
文献类型：
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作者：
VANHILLEGERSBERG, R;VANDENBERG, JWO;WILSON, JHP
研究了使用卟啉前体5-氨基酮丙酸在肿瘤中选择性蓄积的可能性。将同基因结肠癌CC531移植于Wag/Rij大鼠的肝脏。从肿瘤移植后第8天、第14天或第17天开始，每组3至6只动物在饮用水中给予2毫克/毫升的5-氨基乙酰丙酸。另两组在第17天静脉注射Photofrin II(Photomedica Inc.，Raritan，NJ)2.5或5 mg/kg。第19天取肝脏，用溶剂提取和高效液相色谱法测定正常肝脏和肿瘤组织中的卟啉浓度。随着5-氨基酮丙酸给药时间的延长，原卟啉在肿瘤组织中呈进行性蓄积(P=0.0001)，而在正常肝脏中未见增加。给予5-氨基乙酰丙酸11天后，肿瘤与肝脏的卟啉浓度比为4：1。而给予Photofrin II后，正常肝脏中的浓度高于肿瘤(肿瘤与肝脏的比例为1：3)。酶测量显示，与肝脏相比，肿瘤中的铁络合酶活性降低了三倍(P<；0.001)。总之，口服5-氨基乙酰丙酸可导致原卟啉在可移植结肠癌中逐渐积聚，而不会在周围肝组织积聚。这种有选择性的卟啉蓄积似乎是由恶性组织中相对的铁络合酶缺乏引起的。5-氨基乙酰丙酸应用于肝肿瘤的光动力治疗或紫外光荧光早期发现肿瘤可能是一种合适的方法。
The possibility of using the porphyrin precursor 5-aminolevulinic acid to cause selective porphyrin accumulation in tumors was examined. Syngeneic colon carcinomas CC531 were implanted in the livers of Wag/Rij rats. Groups of three to six animals each were given 2 mg/mL of 5-aminolevulinic acid in drinking water from the 8th, 14th, or 17th day after tumor implantation. Two other groups received either 2.5 or 5 mg/kg of Photofrin II (Photomedica Inc., Raritan, NJ) intravenously on day 17. On day 19 the livers were removed and porphyrin concentrations were measured in normal livers and tumors by solvent extraction and high-performance liquid chromatography. Protoporphyrin accumulated progressively in tumors with increasing duration of 5-aminolevulinic acid administration (P= 0.0001), whereas no increase was found in normal livers. After 11 days of 5-aminolevulinic acid administration the porphyrin concentration ratio between tumors and livers was 4:1. In contrast, after Photofrin II administration the concentration was higher in normal livers than in tumors (1:3 ratio, tumor to liver). Enzyme measurements showed a threefold decrease in ferrochelatase activity in tumors compared with livers (P< 0.001). In conclusion, oral administration of 5-aminolevulinic acid results in progressive accumulation of protoporphyrin in a transplantable colon carcinoma without accumulation in the surrounding liver tissue. This selective accumulation of porphyrins appears to be caused by a relative ferrochelatase deficiency in malignant tissue. 5-Aminolevulinic acid administration may be a suitable approach to photosensitizing liver tumors for photodynamic therapy or to early detection of tumors by fluorescence in ultraviolet light.