Published in Cancer Detection and Prevention 1998; 22(Supplement 1).

Oncogenes as predictive biomarkers for low dose radiation carcinogenesis: Potential application for risk assessment

AC Miller, L Lio, EJ Ainsworth, T Seed

Armed Forces Radiobiology Research Institute, Bethesda, MD 20889 USA

AIM: To assess the applicability of radiation-induced oncogenesis as a predictive biomarker in carcinogenesis risk assessment. METHODS: Rodents were irradiated with either low-dose gamma or proton radiation, or implanted with depleted uranium pellets (α-particle emitter). They were then serially euthanized at various times after radiation, and lung, liver, kidney, muscle, or bone tissues were analyzed via northern blot mRNA analysis. DNA was extracted and analyzed for microsatellite instability in some tissues. RESULTS: RNA analysis demonstrated that radiation exposure can induce preneoplastic oncogenic alterations, i.e., increased ras expression, at long times post-radiation, that were time- and radiation quality- dependent. Alterations in p53 status and microsatellite instability in several markers were only observed in animals with radiation-induced lung tumors. CONCLUSIONS: These findings suggest that radiation-induced oncogenesis may be a useful early diagnostic molecular biomarker for carcinogenesis risk assessment.

KEY WORDS: radiation, oncogenesis, biomarker, biomarker, ras, oncogene, risk assessment, depleted uranium, microsatellite, .

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Paper presented at the International Symposium on the Impact of Biotechnology on Prediction, Prevention and Treatment of Cancer; Nice, France; October 24 - 27, 1998; in the section on Risk Identification.