Wang Y, Cheong N, Iliakis G
Thomas Jefferson University, Department of Radiation Oncology and Nuclear Medicine, Philadelphia, Pennsylvania 19107.
Cancer Res. 1993 Mar 15;53(6):1213-7.
We have previously shown that rat embryo fibroblasts expressing the oncogenes H-ras plus v-myc experience a prolonged inhibition of DNA replication after exposure to ionizing radiation as compared to normal rat embryo fibroblasts, or rat embryo fibroblasts expressing H-ras or v-myc alone. Here we show that this enhanced inhibition of DNA replication in cells expressing H-ras plus v-myc is due to inhibition of the main controlling event of DNA replication, i.e., replicon initiation, that this inhibition is reversible, and that the expression of this phenotype is reverted by staurosporine, a protein kinase inhibitor. These findings implicate genetic influences in the processes that control DNA replication in irradiated cells and identify events in the regulation of DNA replication that become apparent several hours after irradiation. The products of the oncogenes H-ras and v-myc appear to be members of, or exert influence on, this controlling pathway.
我们之前已经表明，与正常大鼠胚胎成纤维细胞，或单独表达H-ras或v-myc的大鼠胚胎成纤维细胞相比，表达癌基因H-ras加v-myc的大鼠胚胎成纤维细胞在暴露于电离辐射后经历了DNA复制的长时间抑制。在这里我们表明，在表达H-ras加v-myc的细胞中这种对DNA复制的增强抑制是由于对DNA复制的主要控制事件即复制子起始的抑制，这种抑制是可逆的，并且这种表型的表达可被蛋白激酶抑制剂星形孢菌素逆转。这些发现表明遗传因素在控制受辐射细胞中DNA复制的过程中起作用，并确定了在辐射后数小时变得明显的DNA复制调节事件。癌基因H-ras和v-myc的产物似乎是该控制途径的成员，或对该途径产生影响。
