| Radiation risks in global ecology and human health have attracted more and more attentions along with the rapid development of nuclear energy and nuclear technology, α-particle is an important radiation source in environmental and occupational exposures such as indoor radon and nuclear reactor accident that could induce significant radiation damage. The radiations from nuclear accident always contain a variety of rays including different proportion of a and y-rays. On the other hand, some radioisotopes with a-particle emission are increasingly widespread in cancer treatment, a-particle irradiation has a high linear energy transfer (LET) and possess strong relative biological effectiveness and its influence on human health is one of the forefront in the field of radiobiology research. Since human hematopoietic system is one organ with the highest radiation sensitivity in the body, and the micronucleus is a sensitive indicator of radiation damage, in this study, lymphocyte micronucleus are used to analyze the dose effects of a-particles, y-rays, as well as combination effect of these two irradiations. This study is anticipated to provide new experimental elements for assessing the biological dose of combination radiation and to supply new thinking for radiation protection.Biodosimetery is an important complement to the physical dose of an accident radiation. In order to get some useful information for a rapid and high-throughout biodosimetry. this study also investigated the possibility of y-H2AX and CDKN1A as a biological dosimeter.Part I Dose-responses of micronuclei frequency in lymphocyte irradiated with a-particles and y-raysObjective To investigate the dose-response of micronuclei (MN) frequency in lymphocyte cells irradiated with a-particles and y-rays or their combination and to analyze whether exists any adaptive response between different radiations.Methods Human lymphoblast HMy2.CIR cells were irradiated according to the following conditions:①0.1,0.25,0.5,0.75.1,2,3,4, and5Gy y-ray irradiation;② For a-irradiation, since the short range of a-particle, the cells were cultured in a2.5μm Mylar film-based dish. In order for cell adherence, the Mylar film were coated overnight by polylysine with relative molecular mass of150-300kD before cell incubation. The irradiation dose were0.01,0.025,0.05,0.1.0.15,0.2,0.5,0.75and1Gy;③For the combination exposure, the HMy2.CIR cells were irradiated with0.025,0.1,0.2, or0.5Gy a-particles and then immediately irradiated with0.25,0.75,2,3or4Gy y-rays; Alternatively, the cells were irradiated with0.25,0.75,1, or2Gy y-rays and then were immediately given a-particle irradiation with a dose of0.025,0.1,0.2, or0.5Gy;④The cells were irradiated with2Gy y-ray4h post0.025or0.1Gy a-particle irradiation; Alternatively, the cells were irradiated with0.2or0.5Gy a-particle4h post0.1Gy y-ray irradiation. MN in the irradiated cells was measured with the cytokinesis block (CB) technique. The dose-response curves of MN were established for different radiation situations.Results①For y-ray irradiation, the dose-response of MN was well-fit by the linear-quadratic model with an equation Y=c+aD+βD2.②For α-irradiation, the MN induction increased linearly when the dose was lower than0.25Gy, but when its dose increased continually, the dose-response curve bended and could be well fitted with the BaD model with an equation Y=c+aD+a(1-exp(-5D))exp(-βD) which reflected radiation-induced bystander effect.③For the combination exposure with a-irradiation in the first, the dose-response of MN was similar to that of y-irradiation when the dose of a-particles was lower than0.1Gy, but it was similar to that of a-irradiation when the dose of a-particles was higher. Meanwhile, when the doses of a-particles were0.2and0.5Gy, the MN induction under combination irradiation was significantly higher than that of the sum of corresponding separated irradiation (t=5.22-11.86, P<0.01). For the combination irradiation with0.25Gy y-rays in the first and then0.2,0.5Gy a-particle, the MN induction was significantly higher than the sum of separate irradiation (t=1.92;0.30, P<0.01). When given0.75and2Gy y-ray in the first and then0.2Gy a-particles, the MN yield had no significant difference from the sum of separate irradiation; but wrhen the secondary irradiation of a-particle increased to0.5Gy, the MN induction under combination were higher than the separate irradiation again (t=2.79,4.42, P<0.05). In general, the MN induction induced by the combination exposure with a-particle in the first was higher than that with y-ray in the first.④For the adaptive experiment, it was found that when the interval was4h between two irradiations, a low dose of a-particle irradiation did not induce cell adaptive response to the following γ-ray irradiation but a low dose of γ-rays induced adaptive response to α-particle irradiation.Conclusions The radiation damage of α-particles was different from γ-rays due to the bystander effect. The combination irradiation with α-particle in the first has a synergistic effect on radiation damage. But the combination irradiation with γ-rays in the first was complex and it showed either an antagonistic effect or a synergistic effect when α-irradiation dose was lower than0.2Gy or higher than this dose, respectively. The adaptive response could be stimulated by a low dose of γ-rays but not by a small dose of α particles. Part II:Radiation-induced protein as a potential biological dosimetryObjective To investigate the possibility of DNA repair-related proteins y-H2AX and CDKN1A to be applied for biodosimetry.Methods Human lymphoblast HMy2.CIR cells were irradiated by a-particles or y-rays. The time-responses of the expressions of y-H2AX and CDKN1A were observed. At the time point corresponding to the highest protein expression level, the dose responses of y-H2AX and CDKN1A were measured after0.01～lGy α-particles and0.1-5Gy y-rays irradiation.Results①The first peak time of y-H2AX expression appeared at0.5h and2h of a-particle and y-ray irradiation, respectively. For both irradiations, the expression of y-H2AX was still high at24h post-irradiation. In general, at the peak time, the expression of γ-H2AX increased with the irradiation dose for both a-particles and y-rays.②The expression level of CDKN1A had a peak value at3h after a-irradiation and showed a secondary peak at24h post-irradiation. For y-rays, the expression of CDKN1A protein was increased at24h post-irradiation.Conclusions After α-and γ-ray irradiation, the expressions of γ-H2AX and CDKN1A proteins were relied on the time post-irradiation and the expression level of y-H2AX increased with dose in general. |
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