Talc induces apoptosis in human malignant mesothelioma cells in vitro

Pleurodesis with talc is an accepted method for the treatment of symptomati c 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 effu sion. The possibility that talc may directly affect malignant cells was not considered. The present study was designed to evaluate if talc directly ef fects cell death of malignant mesothelioma cells (MMC) or normal pleural me sothelial 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 deoxynu cleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling (TUNEL) and DNA electrophoresis. Our results demonstrated that talc at a th erapeutically achievable concentration (6 mu g/cm(2)) induces significant a poptosis 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, res pectively) at 48 h, which was significantly (p < 0.05) greater than that in control cells. Electrophoresis of DNA isolated from talc-exposed MMC demon strated the typical ladder pattern of internucleosomal DNA cleavage. Talc d id not induce apoptosis in PMC, and glass beads did not cause significant a poptosis in either MMC or PMC. The present study has demonstrated that talc induces apoptosis in MMC without affecting normal mesothelial cells of the pleura.