Demonstration of a radiation-induced bystander effect for low dose low LET β-particles
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Radiation-induced bystander mutagenesis at a relatively low dose range was investigated using low LET β-particles in a three-dimensional cell culture model. CHO cells were labeled with 0, 0.5, 1.0 or 5.0 μCi tritiated thymidine (3HdTTP) for 12 h and subsequently incubated with AL cells for 24 h at 11°C. The cell mixture was centrifuged to produce a spheroid of 4 × 106 cells of which there was five times more AL than CHO cells. The short-range β-particles emitted by 3HdTTP result in self-irradiation of labeled CHO cells, thus biological effects on neighboring AL cells can be attributed to the bystander response. To evaluate such response, non-labeled bystander AL cells were isolated from among labeled CHO cells and studied independently for survival and mutagenesis. Treatment of CHO cells with 3HdTTP resulted in a dose-dependent increase in bystander mutation incidence among neighboring AL cells compared to controls. In addition, multiplex PCR analysis revealed the types of mutants to be significantly different from those of spontaneous origin. These data provide evidence that low dose low LET radiation can induce bystander mutagenesis in a three-dimensional model. The results of this study will address the relevant issues of actual target size and radiation quality, and are likely to have a significant impact on our current understanding of radiation risk assessment.
KeywordsChinese Hamster Ovary Cell Chinese Hamster Ovary Bystander Effect Tritiated Thymidine Clonogenic Survival
This study was supported by grants from the US Department of Energy DE-FG02-03ER63441 of the Low Dose Program and the National Institutes of Health CA 49062 and ES 11804.
- 1.Bacq ZM, Alexander P (1961) Fundamentals of Radiobiology, 2nd edn. Pergamon Press, OxfordGoogle Scholar
- 2.Nagasawa H, Little JB (1992) Induction of sister chromatid exchanges by extremely low doses of alpha particles. Cancer Res 52:6394–6396Google Scholar
- 16.Hei TK, Piao CQ, He ZY, Vannais D, Waldren CA (1992) Chrysotile fiber is a potent mutagen in mammalian cells. Cancer Res 52:6305–6309Google Scholar
- 18.Williams B, Stender H, Coull JM (2002) PNA fluorescent in situ hybridization for rapid microbiology and cytogenetic analysis. In: Nielsen PE (ed) Nucleic acids: methods and protocols. Humana Press, Totowa, pp 181–193Google Scholar
- 21.Boyd M, Ross SC, Dorrens J, Fullerton NE, Tan KW, Zaultsky MR, Mairs RJ (2006) Radiation induced biologic bystander effect elicited in vitro by targeted radiopharmaceuticals labeled with α, β, and auger electron emitting radionuclides. J Nucl Med 47:1007–1015Google Scholar