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Ionizing radiation is a carcinogen that is known to induce malignant transformation of C3H/10T1/2 fibroblasts in vitro. Radiation is also known to induce c-myc expression and protease inhibitors that suppress radiation transformation reduce myc and fos gene expression. The antiproliferative protein kinase inhibitor 2-aminopurine has been shown to selectively inhibit serum induced c-fos and c-myc expression in human hemopoetic cells. The myc and fos oncogenes are thought to play a role in the regulation of cell proliferation and may be involved in early stages of carcinogenesis. We determined the ability of 2-aminopurine to affect x-ray-induced transformation in C3H/10T1/2 cells in vitro and its effect on myc and fos gene expression in these cells. Treatment with 2-aminopurine (5 x 10(-4) M) resulted in a 50-100% reduction in transformation yield when C3H/10T1/2 cells were irradiated with 6 Gy of x-irradiation. The 2-aminopurine had to be present during the post-confluent stage of cell growth in order to exert its inhibitory effect. Treatment of cells with 2-aminopurine significantly reduced the level of myc gene expression; the inhibitory effect of 2-aminopurine on fos gene expression in these cells was not statistically significant.