Proto-Oncogene Expression: A Predictive Assay for Radiation Biodosimetry Applications

作者：Alexandra C. Miller, Li Luo, Wei-Chiang Chin, Alison E. Director‐Myska, P. G. S. Prasanna, William F. Blakely · 发表于：Radiation Protection Dosimetry · 年份：2002 · DOI：10.1093/oxfordjournals.rpd.a006789 · 被引用次数：21 · 研究领域：Radiopharmaceutical Chemistry and Applications、Chemical Reactions and Isotopes、Computational Drug Discovery Methods

Using a model system of in vitro human peripheral blood lymphocytes, the effect of low-dose (0.25 to 1.50 Gy) 250-kVp X ray radiation (1 Gy.min-1) on the expression of several proto-oncogenes was examined (c-Haras, c-src, c-met, c-jun, c-fos, and c-myc) and beta-actin from 0.25 to 17 h post-radiation. RNA was extracted from cells harvested at various times after exposure and examined for levels of particular mRNAs by northern blot hybridisation. A progressive time- and dose-dependent increase in mRNA levels was observed for c-Haras mRNA, while the other proto-oncogenes (c-src, c-met, c-fos, c-jun and c-myc) examined were variable during the same time period. beta-actin levels were initially decreased but at 17 h post-radiation had returned to control levels. A comparison of the rate of c-Haras transcription at 5 and 17 h post-irradiation revealed that c-Haras transcription was higher at 5 h than at 17 h. These findings suggest that the level of specific proto-oncogene expression, particularly c-Haras, may be useful early diagnostic molecular biomarkers for biodosimetry applications. The use of real-time PCR technologies to quantify gene expression changes will also be discussed.