Proto-oncogene expression: a predictive assay for radiation biodosimetry applications.
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.
Miller
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AC
Applied Cellular Radiobiology Department, Armed Forces Radiobiology Research Institute, 8901 Wisconsin Avenue, Bethesda, MD 20889-5603, USA. millera@mx.afrri.usuhs.mil
Luo
L
L
Chin
W K
WK
Director-Myska
A E
AE
Prasanna
P G S
PG
Blakely
W F
WF
D002467:Cell Nucleus / Q000235:genetics / Q000528:radiation effects; D002478:Cells, Cultured; D004307:Dose-Response Relationship, Radiation; D005786:Gene Expression Regulation / Q000528:radiation effects*; D006801:Humans; D008214:Lymphocytes / Q000528:radiation effects*; D011237:Predictive Value of Tests; D000090063:Proto-Oncogene Mas; D011519:Proto-Oncogenes / Q000528:radiation effects*; D011874:Radiometry / Q000379:methods*; D014158:Transcription, Genetic / Q000528:radiation effects; D014965:X-Rays