Morphological And Molecular Study Of Cell-Chrysotile Interaction In Two Different Cell Lines

Chrysotile accounts for more than 90% of the asbestos used worldwide. This type of fiber is considered the least oncogenic among the asbestos fibers, mainly based on the fiber dimension and biopersistence inside the lung. It is associated with respiratory diseases and lung cancer and identified as human carcinogen by the International Agency for Research on Cancer. However the mechanism and potential of different fibers to cause cancer is still a matter of debate. The present study focuses the interaction of fibers with different cell types, analyzing their ability and mechanism of fiber internalization. After short chrysotile small fibers exposure time (4-8hrs) both non-small cell lung carcinoma and monocytic cell lines were able of fiber internalization. Transmission electron microscope (TEM) analyses showed fibers involved or not by membrane into the cytoplasm and sometimes seemed to be associated with the chromatin. Cytoskeleton elements were observed to be concentrated around the fibers and they were identified as intermediate filaments according to their diameter. Immunofluorescent preparations imaged by laser scanning confocal microscope and submitted to localization analyses showed that both vimentin and cytokeratin may participate in this process. The data suggest that the internalization of fibers may occur through endocytosis and/or by physical perforation of the plasma membrane. Since the scavenger receptors are responsible for recognition and internalization of dust particles by macrophages in lung, and some of them are linked to silica-containing particles recognition we evaluated their expression level of mRNA by using quantitative RT-PCR. The scavenger receptors appear to interfere with the internalization of chrysotile fibers process. SR-A and SCARA5 change their relative expression of mRNA after cell exposure to chrysotile fibers, such as SR-A and SCARA5. Furthermore, our study was the first to find the relationship between the SCARA5 receptor and chrysotile fibers. To check if features of the chrysotile internalization by epithelial and monocytic cells would be related with fibers shape or chemical composition, the cells were exposed to single walled carbon nanotubes in similar conditions. Financial support: FAPESP, CAPES and CNPq) Citation Format: Luana R. Ricardi, Paula Rezende-Teixeira, Marcelo Medina de Souza, Glaucia M. Machado-Santelli. Morphological and molecular study of cell-chrysotile interaction in two different cell lines. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3189. doi:10.1158/1538-7445.AM2014-3189