Radiat Environ Biophys DOI 10.1007/s00411-007-0116-1ORIGINAL PAPER Demonstration of a radiation-induced bystander eVect for low dose low LET -particles

Abstract Radiation-induced bystander mutagenesis at a relatively low dose range was investigated using low LET -particles in a three-dimensional cell culture model. CHO cells were labeled with 0, 0.5, 1.0 or 5.0 Ci tritiated thymi-dine (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 Wve times more AL than CHO cells. The short-range -par-ticles emitted by 3HdTTP result in self-irradiation of labeled CHO cells, thus biological eVects 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 neighbor-ing AL cells compared to controls. In addition, multiplex PCR analysis revealed the types of mutants to be signiW-cantly diVerent 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 signiWcant impact on our current under-standing of radiation risk assessment