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Tumorigenic potential of metal working fluid induced in BALB/c-3T3 transformed cells.
Keshava-N; Lin-F; Chen-ZY; Huffman-D; Ong-T
Environ Mol Mutagen 2001 Mar; 37(Suppl 32):43
Occupational exposures to Metal Working Fluids (MWF) occur in a variety of settings. Workers are exposed to MWF through skin contact and by handling parts, tools and equipment covered with MWF. Our earlier studies indicate that MWF is capable of transforming BALB/c-3T3 cells. Further, studies were performed to identify the tumorigenic potential, if any, of MWF-induced transformed cells in mice. Athymic nude mice, approximately 3-4 weeks, were injected either with MWF-induced transformed cell lines or non-transformed BALB/c-3T3 cells. The mice were observed for tumor formation and sacrificed when the tumor size was between 1-1.5 cm. The tumors were asceptically removed and tumor cell lines were derived. DNA and RNA were isolated from tumor cells and analyzed for genetic alterations. Differential PCR was performed to study gene amplification and expression of several proto-oncogenes (K-ras, c-jun, c-fos, c-myc, c-sis and erb-B2) and tumor suppressor genes (p53 and p16). Random Amplified Polymorphic DNA (RAPD) analysis was carried out to study the genomic changes using 10 different random primers. All mice injected with transformed cells developed tumors within 34 days of injection. Mice injected witih non-transformed BALB/c-3T3 cells did not develop any tumors. None of the genes studied were amplified in tumor cells. However, these cells showed increased expression of c-fos and erb-B2. No significant genomic changes were observed by RAPD analysis. These results indicate that MWF is capable of inducing cellular changes and changes in gene expression of certain oncogenes in BALB/c-3T3 cells and that these cells possess neoplastic potential. Studies are in progress to investigate the molecular mechanism of MWF-induced tumorigenesis.
Cell-transformation; Tumorigenesis; Tumorigens; Metalworking-fluids; Occupational-exposure; Workers; Skin-exposure; Hand-tools; Tools; Laboratory-animals; Animals; Animal-studies
Environmental and Molecular Mutagenesis
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Content source: National Institute for Occupational Safety and Health Education and Information Division