Morphological transformation in vitro of normal human fibroblasts by chrysotile.

Abstract

Pathologic response of tissue to asbestos in vivo gives rise to fibromatoma, granuloma and mesothelioma. We are attempting to develop a model system in vitro using human cells in order to investigate the possible mechanisms responsible for these pathologies.Within the first 12 hr of exposure to chrysotile, the fibroblasts showed distinctive morphological changes. Cells appeared elongated with occasional vacuolated nuclei and granular cytoplasm. Cells showed no other obvious morphological changes by light microscopy and were serially passaged at confluence. The cells with vacuolated nuclei were successfully serially passaged. Binucleated cells were first observed 48 hr after passaging. As time in culture increased (3 days to 2 weeks) many cells lost their distinctive bipolar properties and developed "stress striations" and multiple vacuoles in the cytoplasm. Multinucleated giant cells (2-11 nuclei/cell) with lobate nucleoli became more numerous. With increasing passages, the confluent cell density decreased and cell size increased. Cells usually had condensed nucleoli and had lost all control of directional growth. Preliminary indications suggest that these in vitro morphological transformations are due-at least in part-to a lack of control over cytokinesis.

Morphological Aspects of Interactions between Asbestos Fibers and Human Mesothelial Cell Cytoskeleton

“…Ingested fibers were not lying free in the cytoplasm as reported by Joseph et al [1983] and Richards et al [1977]. Fur thermore the asbestos fibers lead to a de rangement of the cytoskeleton, demon strated by immunofluorescence.…”

In Vitro Assessment of Biopersistence Using Mammalian Cell Systems

“…In vitro acellular systems have been developed to study the release of chemicals from fibers in conditions close to the physiological status (13)(14)(15)(16) (24) and an easy uptake have been reported (25,26). Fibers longer than the cell and extruding fibers often are noted with different cell types (19,(21)(22)(23).…”

An autocrine mitogenic activity produced by a pleural human mesothelioma cell line

“…In order to gain more insight into the biology of this neoplasm, different experimental models have been developed. In vitro experiments with rodent or human mesothelial cells have shown that addition of asbestos fibers to cell cultures has a strong cytotoxic effect and that the surviving cells exhibit various karyotypic abnormalities (Joseph et al, 1983;Lechner et al, 1985;Jaurand et al, 1987). However, although these cells have an expanded life span, they do not induce tumors when injected into nude mice (Lechner et al, 1985).…”