PHOTODYNAMIC-ACTION OF ENDOGENOUSLY SYNTHESIZED PORPHYRINS FROM AMINOLEVULINIC ACID, USING A NEW MODEL FOR ASSAYING THE EFFECTIVENESS OF TUMORAL CELL-KILLING
PHOTODYNAMIC-ACTION OF ENDOGENOUSLY SYNTHESIZED PORPHYRINS FROM AMINOLEVULINIC ACID, USING A NEW MODEL FOR ASSAYING THE EFFECTIVENESS OF TUMORAL CELL-KILLING
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DOI：
10.1016/0020-711x(93)90687-a
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发表时间：
1993-10-01
期刊：
影响因子：
--
通讯作者：
BATLLE, AMC
中科院分区：
文献类型：
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作者：
FUKUDA, H;CASAS, A;BATLLE, AMC
1.采用组织外植体培养技术研究了卟啉类化合物光动力作用的有效性。将小鼠肿瘤组织外植体在含有0.6mM ALA的培养基中孵育1和2小时，在这些条件下合成的总卟啉与我们以前的体内实验中发现的水平相同。然后将外植体用3.5mW输出功率的He-Ne激光照射30分钟，放置在10 cm的距离处。进行了与ALA一起孵育和不与ALA一起孵育的未照射肿瘤组织切片的对照。照射后立即在同一动物的右侧和左侧腹下分别皮下注射恰好1 mm 3的照射和未照射组织的接种物。分别于术后15、20、25天观察肿瘤生长情况.获得的结果表明，与ALA孵育的未辐照对照相比，用ALA孵育1小时并辐照达到2.8 μ g卟啉/g组织浓度的外植体产生了50-70%的肿瘤大小减小。外植体孵育2小时，达到4.6 μ g卟啉/g组织的浓度，产生60%至完全没有肿瘤生长。光照射的有效性指数（EI）计算的基础上，在照射和非照射肿瘤的肿瘤生长。E1接近100%，显示用0.6mM ALA照射2小时的肿瘤几乎完全破坏肿瘤细胞。3.作为细胞损伤和随后的死亡和坏死的指标，测量孵育培养基中的LDH活性和细胞内钾含量。结果表明，作为卟啉负载的肿瘤外植体的照射的结果，发生LDH向培养基的显著释放和细胞内钾的损失。这些发现表明，ALA内源性形成的卟啉与低辐照度激光相结合，可极大地完全破坏肿瘤。
1. The effectiveness of the photodynamic action of porphyrins, was studied by means of the tissue explant culture technique. A murine tumor tissue explant was incubated in a medium containing 0.6 mM of ALA for periods of 1 and 2 hr, total porphyrins synthesized under these conditions were of the same level as those found in our previous in vivo experiments. The explants were then irradiated for 30 min with He-Ne laser of 3.5 mW output power placed at a distance of 10 cm. Controls of non-irradiated tumor tissue slices incubated with and without ALA were performed. Immediately after irradiation, innocula of exactly 1 mm3 of the irradiated and non-irradiated tissue were subcutaneously injected under the right and left flanks of the same animal, respectively. The growth of the tumor was measured 15, 20 and 25 days after implantation.2. Results obtained showed that the explants that were incubated for 1 hr with ALA and irradiated, reaching a concentration of 2.8 mug porphyrins/g tissue, produced a reduction of 50-70% of tumor size as compared with the non-irradiated controls incubated with ALA. Explants incubated for 2 hr, reaching a concentration of 4.6 mug porphyrins/g tissue, produced from 60% to complete lack of tumor growth. The effectiveness index (EI) of photoirradiation was calculated on the basis of the tumor growth in irradiated and non-irradiated tumors. El was nearly 100% showing almost complete tumor cell destruction for tumor irradiated for 2 hr with 0.6 mM ALA. 3. As indicators of cell injury and subsequent death and necrosis, LDH activity in the incubation medium and intracellular potassium content were measured. Results indicated that as a consequence of irradiation of porphyrin loaded tumor explants, significant release of LDH to the medium and loss of intracellular potassium occurred. These findings show great to complete tumor destruction by combination of porphyrins endogenously formed from ALA and low irradiance with laser.