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首页> 外文期刊>Photochemistry and Photobiology: An International Journal >PHOTOSENSITIZATION OF MURINE TUMOR, VASCULATURE AND SKIN BY 5-AMINOLEVULINIC ACID-INDUCED PORPHYRIN
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PHOTOSENSITIZATION OF MURINE TUMOR, VASCULATURE AND SKIN BY 5-AMINOLEVULINIC ACID-INDUCED PORPHYRIN

机译：5-氨基亚麻酸诱导的卟啉对小鼠肿瘤，血管和皮肤的光敏作用

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The effects of topical and systemic administration of 5-aminolevulinic acid (ALA) were examined in several murine tumor systems with regard to porphyrin accumulation kinetics in tumor, skin and blood, vascular and tumor cell photosensitization and tumor response after light exposure. Marked, transient increases in porphyrin levels were observed in tumor and skin after systemic and topical ALA. Rapid, transient, dose-dependent porphyrin increases were also observed in blood; these were pronounced after systemic ALA injection and mild after topical application. They were highest within 1 h after ALA injection, thereafter declining rapidly. This matched the clearing kinetics of injected exogenous protoporphyrin IX (PpIX). initially, vascular photosensitivity changed inversely to blood porphyrin levels, increasing gradually up to 5 h post-ALA, as porphyrin was clearing from the bloodstream. This pattern was again matched by injected, exogenous PpIX. After therapeutic tumor treatment vascular disruption of the tumor bed, while observed, was incomplete, especially at the tumor base. Minimal direct tumor cell kill was found at low photodynamic therapy (PDT) doses (250 mg/kg ALA, 135 J/cm(2) light). Significant, but limited (<1 log) direct photodynamic tumor cell kill was obtained when the PDT dose was raised to 500 mg/kg systemic ALA, followed 3 h later by 270 J/cm(2), a dose that was however toxic to the animals. The further reduction of clonogenic tumor cells over 24 h following treatment was moderate and probably limited by the incomplete disruption of the vasculature. Tumor responses were highest when light treatment was carried out at the time of highest tumor porphyrin content rather than at the time of highest vascular photosensitivity. Tumor destruction did not reach the tumor base, regardless of treatment conditions. [References: 45]
机译：在几个鼠类肿瘤系统中，研究了局部和全身给药的5-氨基乙酰丙酸（ALA）的作用，涉及卟啉在肿瘤，皮肤和血液中的蓄积动力学，血管和肿瘤细胞的光敏性以及光照后的肿瘤反应。在全身和局部ALA后，在肿瘤和皮肤中观察到卟啉水平的显着瞬时增加。在血液中也观察到快速，短暂，剂量依赖性的卟啉增加。全身ALA注射后明显，局部应用后轻度。它们在ALA注射后1小时内最高，此后迅速下降。这与注射的外源原卟啉IX（PpIX）的清除动力学匹配。最初，随着卟啉从血流中清除，血管的光敏性与血卟啉水平成反比，直到ALA后5小时逐渐增加。注入的外源PpIX再次匹配了该模式。在治疗性肿瘤治疗后，观察到的肿瘤床的血管破坏不完全，尤其是在肿瘤底部。在低光动力疗法（PDT）剂量（250 mg / kg ALA，135 J / cm（2）光）下，发现对肿瘤细胞的直接杀伤最小。当PDT剂量提高至500 mg / kg全身性ALA，然后3小时后以270 J / cm（2）剂量照射时，获得了显着但有限的（<1 log）直接光动力学肿瘤细胞杀伤力动物们。治疗后24小时内，克隆性肿瘤细胞的进一步减少是中等的，并且可能受到脉管系统不完全破坏的限制。当在肿瘤卟啉含量最高时而不是在血管光敏性最高时进行光治疗时，肿瘤反应最高。不论治疗条件如何，肿瘤破坏均未到达肿瘤基部。 [参考：45]

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