Inhibition of x-ray induced transformation and effect on myc and fos gene expression by the nucleotide analog, 2-aminopurine.
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.
Sawey
M J
MJ
Department of Radiation Oncology, University of Pennsylvania, School of Medicine, Philadelphia 19104, USA.
Donahue
J
J
Kennedy
A R
AR
D015075:2-Aminopurine / Q000494:pharmacology*; D000818:Animals; D002453:Cell Cycle / Q000187:drug effects / Q000235:genetics; D002455:Cell Division / Q000187:drug effects / Q000235:genetics; D002460:Cell Line; D002471:Cell Transformation, Neoplastic / Q000187:drug effects* / Q000235:genetics / Q000528:radiation effects*; D015870:Gene Expression / Q000187:drug effects / Q000528:radiation effects; D016762:Genes, fos / Q000187:drug effects* / Q000528:radiation effects; D016259:Genes, myc / Q000187:drug effects* / Q000528:radiation effects; D006801:Humans; D051379:Mice
D015075:2-Aminopurine