Abstract:
Astronauts travelling in space will be exposed to mixed beams of particle radiation and photons. Exposure limits that correspond to defined cancer risk are calculated by multiplying absorbed doses by a radiation-type specific quality factor that reflects the biological effectiveness of the particle without considering possible interaction with photons. We have shown previously that alpha radiation and X-rays may interact resulting in synergistic DNA damage responses in human peripheral blood lymphocytes but the level of intra-individual variability was high. In order to assess the variability and validate the synergism, blood from two male donors was drawn at 9 time points during 3 seasons of the year and exposed to 0-2 Gy of X-rays, alpha particles or 1:1 mixture of both (half the dose each). DNA damage response was quantified by chromosomal aberrations and by mRNA levels of 3 radiation-responsive genes FDXR, CDKN1A and MDM2 measured 24 h post exposure. The quality of response in terms of differential expression of alternative transcripts was assessed by using two primer pairs per gene. A consistently higher than expected effect of mixed beams was found in both donors for chromosomal aberrations and gene expression with some seasonal variability for the latter. No synergy was detected for alternative transcription.
摘要:
在太空中旅行的宇航员将暴露于粒子辐射和光子的混合束。与定义的癌症风险相对应的暴露极限是通过将吸收剂量乘以反映粒子的生物学有效性的辐射类型特定质量因子来计算的,而不考虑与光子的可能相互作用。我们先前已经表明,α辐射和X射线可能相互作用,从而在人外周血淋巴细胞中产生协同的DNA损伤反应,但个体内变异性水平很高。为了评估变异性并验证协同作用,在一年中的3个季节中的9个时间点抽取两名男性捐献者的血液,并暴露于0-2Gy的X射线中,α粒子或两者的1:1混合物(每个剂量的一半)。通过染色体畸变和3个辐射响应基因FDXR的mRNA水平定量DNA损伤反应,CDKN1A和MDM2在暴露后24小时测量。通过使用每个基因两个引物对评估替代转录物的差异表达方面的响应质量。在两个供体中,混合束的染色体畸变和基因表达的效果始终高于预期,而后者则具有一定的季节性变异性。对于替代转录没有检测到协同作用。