Mutagenesis & Carcinogenesis

Monday, October 17, 2005 1:30 PM-3:00 PM Room No. 603
Chair(s): Giaccia, Amato; Barcellos-Hoff, Mary Helen

(MS032) Neoplastic transformation in vitro induced by low doses of 232 MeV protons.

Elmore, Eugene*,1, Lao, Xiao-Yan1, Ko, Micki1, Kapadia, Rubina1, Rightnar, Steven2, Nelson, Gregory2, Redpath, Les 1, 1 Radiation Oncology, Irvine, CA, USA2 Loma Linda University Proton Therapy Facility, Loma Linda, CA, USA

ABSTRACT- Introduction. Over the past several years we have demonstrated that low doses (≤ 100 mGy) of low LET radiation (Cs-137 gamma rays, 60 kVp x-rays, 28 kVp x-rays) can suppress neoplastic transformation in vitro of Hela x skin fibroblast human hybrid cells to values below that seen spontaneously. We have also determined that the underlying mechanisms are likely to include hyper-radiosensitivity of a subpopulation of cells that are prone to in vitro transformation as well as, at somewhat higher doses, the induction of radioresistance. Results. Under the auspices of funding from the DOE Low Dose Radiation Research Program, and with assistance from NASA, we have now performed five repeat experiments with a high energy proton beam (232 MeV, mean LET 0.44 keV/micron) at Loma Linda University. The doses we examined were 5, 50, 100, 300 and 600 mGy. The data indicate no evidence for induction of transformation at doses ≤ 100 mGy. At doses of 5 and 50 mGy there is evidence for a possible suppression of transformation frequencies below that seen spontaneously. Conclusion. The shape of the dose response curve does not follow a linear no-threshold model. Supported by the Office of Science (BER), U. S. Department of Energy, Grant No. DE-FG02-03ER63648. Protons were provided by the Loma Linda University Proton Treatment facility under funding by NASA cooperative agreement NCC9-149.

Key words: neoplastic transformation, high energy protons, low doses

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2005 RRS