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Alterations of cancer-related genes in tumor cell lines derived from cadmium-transformed BALB/c-3T3 cells.
Joseph P; Muchnok TK; Zhou G; Ong T; Whong WZ
Environ Mol Mutagen 2000 Jan; 35(Suppl 31):33
The International Agency for Research on Cancer (IARC) has classified cadmium as a human carcinogen. A large number at workers are potentially exposed to this metal in various occupational settings. Considering the lack at information regarding the molecular mechanism(s) at cadmium carcinogenesis, studies were conducted to investigate the changes in copy number and expression at various cancer-related genes as a possible mechanism for carcinogenesis due to exposure to cadmium. BALB/c-3T3 cells were morphologically transformed with cadmium and the transformed cells were subcutaneously injected into nude mice to develop tumors. Cell lines established from these tumors were used in the present study. Differential PCR and RT-PCR were employed to determine changes in copy number and expression at p53, p16, K-ras, c-myc, c-fos, c-jun, c-sis and erbB1. Tumor cell lines showed a decrease in gene copy number and expression of p16 and erbB1 compared to the control BALB/c-3T3 cells. Gene copy number and gene expression of c-fos and c-jun were significantly higher in the tumor cell lines compared to those of the control cells. In spite of a significant increase in gene copy number of K-ras in tumor cells, no change was observed in its expression. Neither the copy number nor the expression of c-myc exhibited any significant change in the tumor cell lines. These results indicate that the observed changes in gene copy number and gene expression of the cancer-related genes may be at least partly responsible for the cellular transformation induced by cadmium.
Genes; Cancer; Tumors; Cadmium-compounds; Carcinogens; Carcinogenicity; Carcinogenesis; Workers; Work-environment; Occupational-exposure; Metals; Laboratory-animals; Animals; Animal-studies; Cell-transformation
Environmental and Molecular Mutagenesis
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