Fibach E, Rachmilewitz E A, Gatt S
Department of Hematology, Hadassah University Hospital, Jerusalem, Israel.
Res Exp Med (Berl). 1992;192(3):185-96. doi: 10.1007/BF02576274.
The effects of photochemotherapy with the fluorescent fatty acid pyrenedodecanoic acid (P12) and long-wavelength ultraviolet (UVA) light on cells derived from human bladder carcinoma were studied. Exposure of these anchorage-dependent cells to P12 either in monolayers of adherent cells or in suspension resulted in a time-related uptake of P12 and its incorporation into the cells' neutral and phospholipids. The uptake and localization of P12 was visualized with fluorescence microscopy and the distribution of the cell population with respect to P12 uptake was analyzed by flow cytometry. Irradiation of P12-containing monolayers of bladder carcinoma cells with UVA light resulted in cell killing. But, on microscopic examination no apparent cell lysis was detected, and since digestion with trypsin did not result in the dispersion of the monolayers it was impossible to assess toxicity by cell count. Alternative procedures were therefore used, and the following cell parameters were determined: (a) cellular uptake or release of chromate; (b) ability of cells to re-adhere to the substratum; and (c) the long-range proliferation potential. The combined inhibitory effect of photoirradiation on cell adherence and on their proliferative potential was utilized for determining reductions of up to 7 log in cell viability. The results obtained with five independently established in vitro bladder carcinoma cell lines indicated that these cells are susceptible to P12-induced photosensitization, suggesting that bladder malignancies might be potential candidates for pyrene-induced photochemotherapy.
研究了荧光脂肪酸芘十二烷酸(P12)和长波紫外线(UVA)光的光化学疗法对人膀胱癌细胞系的影响。将这些贴壁依赖性细胞暴露于单层贴壁细胞或悬浮液中的P12中,会导致P12随时间摄取并掺入细胞的中性和磷脂中。用荧光显微镜观察P12的摄取和定位,并用流式细胞术分析细胞群体相对于P12摄取的分布。用UVA光照射含P12的膀胱癌细胞单层导致细胞死亡。但是,在显微镜检查中未检测到明显的细胞裂解,并且由于用胰蛋白酶消化不会导致单层细胞分散,因此无法通过细胞计数评估毒性。因此采用了替代方法,并测定了以下细胞参数:(a)细胞对铬酸盐的摄取或释放;(b)细胞重新粘附于基质的能力;(c)长期增殖潜力。光照射对细胞粘附及其增殖潜力的联合抑制作用用于确定细胞活力降低多达7个对数。用五个独立建立的体外膀胱癌细胞系获得的结果表明,这些细胞对P12诱导的光致敏敏感,这表明膀胱恶性肿瘤可能是芘诱导的光化学疗法的潜在候选对象。