Occupational exposure to tetrachloroethylene (TCE) occurs in a number of settings in which organic solvents are used, particularly the dry-cleaning industry. Phenotypic and genotypic changes during carcinogenesis may be demonstrated by the cell transformation and tumorigenesis assays and by molecular analyses. To study the carcinogenic potential of TCE, BALB/c-3T3 cells were exposed to TCE at varying concentrations for 24 hours. Further, nude mice were injected with TCE-transformed cells. TCE caused a significant increase in transformation frequency in a dose dependent manner. Also, the cytotoxicity data indicated a dose-dependent decrease in the cell number after TCE treatment. All the mice injected with transformed cells developed tumors indicating the tumorigenic potential of TCE. DNA from both transformed and tumor cells derived from transformed cells were subjected to differential PCR to detect changes in gene copy number and gene expression of five proto-oncogenes (K-ras, c-fos, c-jun, sis, erb-B2) and two tumor supressor genes (p53, p16). While none of the transformed cells showed changes in gene amplification, increases in the expression of c-jun and p16 were observed and sis was under expressed. Tumor cells showed increased copy number of the K-ras gene and increased expression of c-fos, erbB2 and K-ras, while c-myc and sis were under expressed. These results indicate that TCE is capable of inducing cellular and molecular changes in BALB/c-3T3 cells and that these cells then possess neoplastic potential. Further studies are in progress to investigate the molecular mechanism of TCE-induced cell transformation and tumorigenesis.
The Toxicologist. Society of Toxicology 40th Annual Meeting, March 25-29, 2001, San Francisco, California