PATTERNS OF C-FOS AND C-JUN PROTOONCOGENE EXPRESSION, APOPTOSIS, AND PROLIFERATION IN RAT PLEURAL MESOTHELIAL CELLS EXPOSED TO ERIONITE OR ASBESTOS FIBERS

Erionite, a naturally occurring fibrous zeolite, is associated with th e development of nonmalignant and malignant lung diseases and is more carcinogenic than asbestos fibers in man and rodent inhalation models of disease. To investigate the possible molecular mechanisms of erioni te-induced toxicity and carcinogenesis and whether cationic content of erionite fibers was important, we examined c-fos and c-jun mRNA level s, activator protein-1 (AP-1) binding to DNA, and changes in cell prol iferation and apoptosis in rat pleural mesothelial (RPM) cells exposed to different cation-substituted erionite fibers or crocidolite asbest os at various concentrations (1, 5, or 10 mu g/cm(2) dish) at time per iods from 8 to 48 h after addition of minerals. c-fos mRNA levels in c ells exposed to equal weight concentrations of various erionites and c rocidolite fibers were increased comparably. When compared to other fi bers, Na-erionite caused significantly increased levels of c-jun mRNA at lower mass concentrations (1 and 5 mu g/cm(2)) than crocidolite asb estos, but comparable AP-1 binding to DNA. In comparison to untreated controls, numbers of RPM cells incorporating 5'-bromodeoxyuridine (Brd U) were increased dramatically after exposure to asbestos or Na-erioni te at 5 and 10 mu g/cm(2). Significant dose-dependent increases in apo ptosis were observed with asbestos at all time points, whereas erionit es failed to induce apoptosis at 8 or 24 h, with minimal induction at higher concentrations than asbestos at 48 h. These data suggest that e rionite increases the balance between cell proliferation (and/or abnor mal DNA repair) and apoptosis, a normal mechanism of elimination of tr ansformed Or proliferating cells. (C) 1998 Academic Press.