MECHANISMS OF PORPHYRIN ACCUMULATION BY CANCEROUS CELLS

卟啉光疗已被用于治疗某些疾病，并取得了一些成功 肿瘤，包括其他无法手术的支气管癌。 荧光灯照射时，癌细胞中的防御素积聚， 能够检测到加载了卟啉的癌细胞，还可以产生 局部的杀瘤作用。生化机制及其后果 卟啉与正常和癌组织细胞成分相互作用的研究 组织还没有得到充分的评估。卟啉结合蛋白和 卟啉代谢酶很可能是导致 卟啉的细胞积聚或消除 “封闭水库”或改变外源卟啉的新陈代谢。 此外，通过与重要的细胞成分相互作用，外源 卟啉可能会影响正常组织。 其中一个目标是鉴定和定量细胞前卟啉结合蛋白。 在正常组织和肿瘤组织中。最初的重点将放在 几种卟啉使用后胞浆谷胱甘肽-S转移酶的变化 临床上抑制这些酶。涉及的蛋白质将被分离出来 通过亲和层析，并用于提高抗体为后续 在感兴趣的组织中进行鉴定和定量。另一个目标是 目的：评价外源性卟啉的代谢。细胞内 卟啉的新陈代谢可能会影响细胞对它们的保留，因为 卟啉往往会在组织中积聚，而这些组织不容易 让它们代谢。外源性卟啉对大鼠血管紧张素转换酶的不同影响 线粒体铁络合酶和相当低的该酶水平 在Morris肝癌组织中已发现7288C比正常肝组织。这个 外源卟啉与铁络合酶及其相互作用的研究 血红素加氧酶的类似物，以及这些酶的活性 将对正常组织和癌组织进行测量。对细胞的影响 正常细胞暴露于外源性卟啉的代谢也将 评估过了。Morris肝癌被用作模型系统，因为这些 细胞可以在培养中生长，也可以在大鼠体内作为实体瘤生长。此外, 它们是来自肝脏的细胞，它们的新陈代谢可以与 正常的肝脏，它在卟啉代谢中起着至关重要的作用。素数 目的是在人类肿瘤的基础上进行类似的研究 在与老鼠的研究中开发的知识和工具。

Porphyrin phototherapy has been used with some success to treat certain neoplasias, including otherwise inoperable cancers of the bronchus. Prophyrins accumulated in cancerous cells when illuminated fluoresce, enabling detection of porphyrin-loaded cancerous cells and also produce localized tumoricidal effects. The biochemical mechanisms and consequences of porphyrin interactions with cellular components of normal and cancerous tissues have not been fully assessed. Porphyrin-binding proteins and porphyrin-metabolizing enzymes are likely to be important factors in the cellular accumulation or elimination of porphyrins acting either as "trapping reservoirs" or altering the metabolism of exogenous porphyrins. Moreover, by interacting with important cellular components, exogenous porphyrins are likely to affect normal tissues. One aim is to identify and quantitate cellular prophyrin-binding proteins in normal and neoplastic tissues. The initial focus will be on the cytosolic glutathione-S-transferases since several porphyrins used clinically inhibit these enzymes. The proteins involved will be isolated by affinity chromatography and used to raise antibodies for subsequent identification and quantitation in the tissues of interest. Another aim is to evaluate the metabolism of exogenous porphyrins. Intracellular metabolism of porphyrins is likely to affect their retention by cells since porphyrins would tend to accumulate in tissues which cannot readily metabolize them. Differential effects of exogenous porphyrins on mitochondrial ferrochelatase and considerably lower levels of this enzyme in Morris hepatoma 7288 C tissue than normal liver have been found. The interaction of exogenous porphyrins with ferrochelatase and of their heme-analogs with heme oxygenase, and the activity of these enzymes in normal and cancerous tissues will be measured. The effects on cellular metabolism of exposure of normal cells to exogenous porphyrins will also be assessed. The Morris hepatoma is used as a model system because these cells can be grown in culture or as a solid tumor in rats. In addition, they are liver-derived cells and their metabolism can be compared with normal liver, which plays a vital role in porphyrin metabolism. A prime objective is to carry out similar research with human tumors based on the knowledge and tools developed in the studies with the rat.