Effects of crocidolite fibers on the peritoneal mesothelium of rats

The assay of intraperitoneal (ip) injection to rats was used as experimenta l system to study the mechanisms of carcinogenic effects of fibrous dusts, with this test system, fibers were shown to induce mesothelioma in the peri toneal cavity Although the data of the ip assay are discussed controversial ly in terms of risk assessment, it is a valuable tool to investigate the mo lecular mechanisms of mesothelioma carcinogenesis in vivo. This test system allows one to investigate both the effects of fibers on signal transductio n and the genotoxic potential of fibers. On the level of mRNA expression, d ifferent stages of fiber-induced tumor development in the peritoneal space were examined using differential display techniques. Genes of signal transd uction pathways are mainly affected by the fiber treatment; for example, th e activation of genes for the AP-I transcription factor could be observed i n the tissues of the peritoneal cavity Thus, our in vivo data confirm the f indings reported from cell culture systems. Moreover, our results from the differential display assays reveal that genes involved in the integrin-link ed signal transduction are upregulated. in addition, the ip assay can be ap plied to transgenic animals to perform mutagenicity testing. Using the Big Blue transgenic animal system, we provide data of a significant increase in mutation frequency after treatment with crocidolite asbestos.