The Biological Effectiveness of Radon-Progeny Alpha Particles. IV. Morphological Transformation of Syrian Hamster Embryo Cells at Low Doses

Primary explants of Syrian hamster embryo (SHE) cells were exposed to either low-LET 250 kVp X rays or graded single doses of defined high-LET α particles (90, 100, 120, 150, 180 and 200 keV/μm), simulating those produced by radon progeny, and monitored for cell inactivation and oncogenic transformation. For the α particles the doses delivered ranged from 1 cGy to 1 Gy with an emphasis on doses less than 20 cGy, while for the X rays the doses ranged from 20 cGy to 4 Gy. The dose-response curves for cell killing by α particles approximated an exponential function of dose, whereas the X rays produced a curve with a shoulder characteristic of linear-quadratic relationships seen for low-LET radiations. The RBE at 10% survival varied between 3.6-7.0 depending on the LET of the α particles, with the${\rm RBE}_{{\rm m}}$ ranging between 7-12. The most effective α particles were those with an LET of 120 keV/μm. All radiations produced initial increases in the frequency of morphological transformants, as a function of dose, with a rise to a maximum followed by a plateau in the response which was relatively constant at approximately$2-6\times 10^{-3}$ transformants per initial cell at risk. At higher doses the transformation frequency, expressed per initial cell at risk, had a tendency to decline to parallel the cell survival response. Both the dose at which the maximum frequency of transformants was expressed and the initial slope of the dose-response relationship differed substantially between the different radiation qualities. Maximal transformation per initial cell at risk occurred at doses as low as 1-4 cGy for the 90 and 100 keV/μm particles with the maximum occurring at higher doses (to 16 cGy) as the LET increased toward 200 keV/μm. In contrast, the maximal transformation for 250 kVp X rays was at 50 cGy. The 90 and 100 keV/μm particles, with an${\rm RBE}_{{\rm m}}$ of 60 and 37, respectively, based on the ratios of the initial slopes of the dose-response curves, were the most effective LETs in terms of the ability to induce morphological transformation of SHE cells. When expressed in terms of particle fluence, it appears that in the LET range of radon progeny approximately two to four particle traversals per nucleus are required per killing event, whereas it is at doses corresponding to less than one particle per nucleus that maximal oncogenic transformation is expressed. Environmentally relevant radon levels result in human exposure to lung doses that are sufficiently low that the likelihood that a cell will be traversed by two or more α particles is rare. That is, the majority of cells lining the lung are unaffected and those that are hit suffer one α particle per cell nucleus. This situation corresponds to these findings, where maximal oncogenic transformation is expressed at fluence levels where the majority of cell nuclei experience either no or one α particle.