Nasreen N, Mohammed K A, Dowling P A, Ward M J, Galffy G, Antony V B
Division of Pulmonary and Critical Care Medicine, Department of Medicine, Veterans' Affairs Medical Center, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA.
Am J Respir Crit Care Med. 2000 Feb;161(2 Pt 1):595-600. doi: 10.1164/ajrccm.161.2.9904123.
Pleurodesis with talc is an accepted method for the treatment of symptomatic pleural effusions secondary to mesotheliomas. Patients with mesothelioma who have talc-induced pleurodesis have a lower morbidity than do those who do not have pleurodesis. The mechanisms whereby talc mediated these effects were considered to be secondary to a decrease or absence of a pleural effusion. The possibility that talc may directly affect malignant cells was not considered. The present study was designed to evaluate if talc directly effects cell death of malignant mesothelioma cells (MMC) or normal pleural mesothelial cells (PMC). Three confluent MMC and PMC were exposed to talc for 24, 48, and 72 h. In parallel experiments, glass beads similar in size to talc were included as control. Apoptosis was determined by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling (TUNEL) and DNA electrophoresis. Our results demonstrated that talc at a therapeutically achievable concentration (6 microg/cm(2)) induces significant apoptosis in MMC. Talc-induced maximum apoptosis in MMC (39.50 +/- 2.55%, 31.87 +/- 4.69%, and 15.10 +/- 3.93% in CRL-2081, CRL-5820, and CRL-5915, respectively) at 48 h, which was significantly (p < 0.05) greater than that in control cells. Electrophoresis of DNA isolated from talc-exposed MMC demonstrated the typical ladder pattern of internucleosomal DNA cleavage. Talc did not induce apoptosis in PMC, and glass beads did not cause significant apoptosis in either MMC or PMC. The present study has demonstrated that talc induces apoptosis in MMC without affecting normal mesothelial cells of the pleura.
滑石粉胸膜固定术是治疗间皮瘤继发症状性胸腔积液的一种公认方法。接受滑石粉诱导胸膜固定术的间皮瘤患者的发病率低于未接受胸膜固定术的患者。滑石粉介导这些作用的机制被认为是继发于胸腔积液的减少或消失。滑石粉可能直接影响恶性细胞的可能性未被考虑。本研究旨在评估滑石粉是否直接影响恶性间皮瘤细胞（MMC）或正常胸膜间皮细胞（PMC）的细胞死亡。将三株融合的MMC和PMC暴露于滑石粉中24、48和72小时。在平行实验中，将尺寸与滑石粉相似的玻璃珠作为对照。通过末端脱氧核苷酸转移酶介导的脱氧尿苷三磷酸缺口末端标记（TUNEL）和DNA电泳来确定细胞凋亡。我们的结果表明，治疗可达到的浓度（6μg/cm²）的滑石粉可诱导MMC发生显著凋亡。滑石粉诱导MMC的最大凋亡率（CRL-2081、CRL-5820和CRL-5915分别为39.50±2.55%、31.87±4.69%和15.10±3.93%）在48小时时出现，显著高于对照细胞（p<0.05）。从暴露于滑石粉的MMC中分离的DNA电泳显示出典型的核小体间DNA裂解梯形模式。滑石粉未诱导PMC凋亡，玻璃珠在MMC或PMC中均未引起显著凋亡。本研究表明，滑石粉可诱导MMC凋亡，而不影响胸膜的正常间皮细胞。
