Megnin F, Faustino P J, Lyon R C, Lelkes P I, Cohen J S
Biochim Biophys Acta. 1987 Jul 6;929(2):173-81. doi: 10.1016/0167-4889(87)90173-x.
Comparative studies of the toxicity, stability, and retention of the water-soluble porphyrin, tetraphenylporphyrin sulfonate (TPPS), and its complex with Mn(III), have been made with the human breast cancer cell line MCF-7 wild type, and an adriamycin-resistant line derived from it, termed AdrR. Based on growth inhibition, we determined the maximum non-toxic concentration of MnTPPS tolerated by these cells. The integrity of MnTPPS in vitro was investigated by fluorescence microscopy, and we found that there is very little dissociation of MnTPPS within these cells within 4 days. We report novel proton magnetic resonance relaxation measurements of the bulk water of cells in a gel matrix undergoing perfusion. A slightly greater net uptake of MnTPPS in the wild-type cells was observed compared to AdrR; however, there was no significant difference in retention of MnTPPS. These results indicate that over a period of several hours the mechanism of selective retention of these compounds in tumour cells is not due to specific interaction with heme-binding protein, of which there is enhanced expression in the resistant cells. The fact that the net rate of washout of MnTPPS is approximately the same as the net rate of uptake also appears to eliminate compartmentalization or enzymatic modification of MnTPPS within these cells.
对水溶性卟啉四苯基卟啉磺酸盐（TPPS）及其与锰（III）的络合物的毒性、稳定性和滞留情况进行了比较研究，研究对象为人乳腺癌细胞系MCF - 7野生型及其衍生的阿霉素耐药系AdrR。基于生长抑制情况，我们确定了这些细胞所能耐受的MnTPPS的最大无毒浓度。通过荧光显微镜研究了MnTPPS在体外的完整性，我们发现在4天内这些细胞内MnTPPS几乎没有解离。我们报告了在进行灌注的凝胶基质中对细胞体相水进行的新型质子磁共振弛豫测量。与AdrR相比，野生型细胞中观察到MnTPPS的净摄取量略高；然而，MnTPPS的滞留情况没有显著差异。这些结果表明，在数小时的时间段内，这些化合物在肿瘤细胞中选择性滞留的机制并非由于与血红素结合蛋白的特异性相互作用，而在耐药细胞中血红素结合蛋白的表达有所增强。MnTPPS的净洗脱速率与净摄取速率大致相同这一事实似乎也排除了这些细胞内MnTPPS的区室化或酶促修饰。
