Design, spectrum measurements and simulations for a 238Pu α-particle irradiator for bystander effect and genomic instability experiments
Introduction
According to the target theory of radiation-induced effects, which is the core of radiation biology, DNA damage occurs during or very shortly after irradiation of the nuclei in targeted cells, and the potential for radiobiological consequences can be expressed within one or two cell generations. However, “non-(DNA)-targeted” effects, such as radiation-induced bystander effect and genomic instability, challenge the theory that attributes radiation-induced effects solely to targeted damage to DNA. These effects occur without direct exposure of the nucleus to radiation, and they are particularly significant at low doses.
Chromosomal instability has been recently demonstrated in clonal descendants of hemopoietic stem cells in murine bone marrow irradiated with α-particles (Kadhim et al., 1992; Lorimore et al., 1998). Lorimore et al. (1998) irradiated bone marrow cells from male mice with α-particles using a versatile source containing a 20-mm-diameter disc of 238Pu (Goodhead et al., 1991). The irradiations were performed with and without a rectangular grid made of brass wires (0.34 mm in diameter); the survival of the traversed clonogenic cells was studied using the CFU-A assay. It was found that the increase in the survival of clonogenic cells irradiated behind the grid was consistent with the reduction in the exposed area due to the grid (according to confocal microscopy, the motion of the cells was negligible). However, the number of the colonies expressing chromosomal instability did not decrease. Thus, α-particles induced chromosomal instability, but the instability also occurred in the progeny of unirradiated stem cells, which must be due to unexpected interactions between the irradiated and unirradiated cells (bystander effect).
Genomic instability in the form of delayed micronucleation, apoptosis and reproductive death has been further observed in the progeny of human fibroblasts irradiated with X-rays and α-particles (Belyakov et al., 1999). α-Particles turned out to be more effective than X-rays (per unit dose) in terms of both the initial and delayed responses, including apoptosis. The α-particles were produced by a 238Pu-based irradiator similar to that described by Goodhead et al. (1991).
In this paper, we report results of simulations and measurements of α-particle energy spectra of a newly built 238Pu-based irradiator, which will be used to study direct and non-targeted effects of exposure to α-particles in cell cultures and 3D human tissue systems. The simulations were necessary because α-particle energy spectra could not be measured with a high-resolution spectrometer under the operational conditions of the irradiator, where He gas (in equilibrium with the ambient air in terms of pressure and temperature) is used as the medium between the source and the exit window of the irradiator.
Section snippets
Irradiator
The design of our irradiator in the present broad-beam mode of operation conforms to that described by Goodhead et al. (1991), except for the specimen wheel, sector plate and aperture disc (Fig. 1). The α-particle source of the irradiator is housed in a stainless steel tube 60 cm in height and 15 cm in diameter. In order to reduce the α-particle energy losses and to increase the average range of the α-particles, the housing is flushed with He gas instead of air (or nitrogen). When the irradiator
Results and discussion
Fig. 2 shows results of the measurements and of the corresponding simulations. The observed shift of the α-particle spectrum mean energy caused by the 2-μm PET foil is correctly reproduced by the simulations when the thickness of the Cr7C3 layer is set to 0.88 μm and the density of the PET foil is specified as 1.32 g cm−3. In order to reproduce the FWHMs of the measured spectra, we introduced a Gaussian 16% (1σ) fluctuation of the thickness of the Cr7C3 layer. The low-energy tails in the measured α
Acknowledgements
The authors wish to thank Seppo Klemola at STUK—Radiation and Nuclear Safety Authority for the gamma spectrometric measurements.
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