Decreased apoptosis in tumor cells and transformed cells induced by cadmium chloride and beryllium sulphate.
Keshava-N; Lin-F; Whong-WZ; Ong-T
Environ Mol Mutagen 2000 Apr; 35(Suppl 31):35
Imbalance in the process of cell proliferation, differentiation and programmed cell death (apoptosis) is involved in carcinogenesis. It is postulated that inhibition of apoptosis may help altered cells escape cell death and acquire a tumorigenic phenotype. In our previous study, BALB/c-3T3 cells were transformed with either cadmium chloride (CdCI2) or beryllium sulphate (BeSO4). Transformed cells were injected into nude mice and tumor cell lines were established. In the present study, we have induced apoptosis in non-transformed, transformed and tumor cells induced by CdCI2 and BeSO4 using actinomycin D. Apoptosis was measured using terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling [TUNEL] assay and enzyme-linked immuno-sorbent assay [ELISA]. Immuno-staining indicates that there was increased apoptosis in the nontransformed cells compared to transformed cells, and that transformed cells had a higher percentage of apoptotic cells compared to tumor cells. Similar results were obtained in the ELISA assay. It is possible that the neoplastically transformed cells induced by CdCI2 and BeSO4 may have undergone molecular changes allowing them to bypass apoptosis or they may not have accumulated enough genetic damage to induce an apoptotic response. Further studies are in progress to investigate the involvement of apoptosis-related genes (BcI2, Bax, Bel-Xi. Bak) in the process of transformation and/or tumorigenesis.
Tumors; Cell-transformation; Cell-damage; Carcinogenesis; Carcinogens; Laboratory-animals; Animals; Animal-studies; Tumorigens; Tumorigenesis
Abstract; Conference/Symposia Proceedings
Environmental and Molecular Mutagenesis