Transforming and tumorigenic potential of tetrachloroethylene in BALB/c-3T3 cells.
Keshava N; Lin F; Whong WZ; Ong TM
Mutat Res 2001 Oct; 483(Suppl 1):S83
Exposure to tetrachloroethylene (TCE) occurs in a number of occupational settings such as during dry-cleaning and metal degreasing. 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 transformed cells were subjected to differential PCR to detect changes in gene copy number and gene expression of six protooncogenes (K-ras, c-fos, c-jun, c-myc, c-sis, erb-B2) and two tumor suppressor genes (p53, p16). While none of the transformed cells showed changes in gene amplification, altered gene expression was observed in c-jun, c-sis and p16. 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 epigenetic mechanism(s) of TCE-induced cell transformation and tumorigenesis.
Exposure-levels; Carcinogenesis; Cell-transformation; Tumorigenesis; Animal-studies; Tumors; Tumorigens; Occupational-exposure; Dry-cleaning-industry; Carcinogenicity; Carcinogens; Exposure-assessment; Laboratory-animals; Animals
Toxicology and Molecular Biology Branch, NIOSH, 1095 Willowdale Road, Morgantown, WV 26505