The Somatic Cell Mutations At The Glycophorin A Locus In Erythrocytes Of Medical Radiation Workers

Ionizing radiation (IR) is a common environmental carcinogen, and it can induce genomic DNA damage. The glycophorin A(GPA)mutation assay is one of somatic mutation assays. It can provide lifetime biological dosimetry of environmental carcinogens because the mutations are acculumated in bone marrow stem cells. Thus, it can be used to estimate cumulative dose of environmental carcinogens and to assess the cancer risk of humans exposed to environmental carcinogens including radiation. But so far, there are few studies on these affecting factors on the GPA mutation frequency as a biological marker of the cumulative effects and cancer risk of chronic low doses of ionizing radiation.The subjects were recruited from336medical radiation workers who are working in the department of Radiology of different hospitals of shanghai and112adult healthy subjects, and a self-administered questionnaire which including general information on individuals, the history of radiation exposure and so on, was obtained, and peripheral blood was collected from all of the subjects in heparin-treated tubes. Erythrocytes were isolated, fixed in formalin and immune-labeled with fluorescent antibodies (anti-M,6A7-PE; anti-N, BRIC-157, IBGRL) that are specific for the two allelic forms of the cell surface GPA protein, followed by flow cytometry analysis. The individual genetic susceptibility was investigated by using Cytokinesis-block micronuclei and3AB index. The dose-effectiveness curve of peripheral lymphocyte micronucleus induced by irradiation was constructed in this laboratory. Meanwhile, the total cumulative exposure doses as the contact exposure index of medical radiation workers were estimated by using the standard micronuclei dose-effectiveness curve which was constructed in this laboratory, and investigate the occurence of micronucleus of medical radiation workers, GPA mutation frequency and related factors. The followings are the primary results of the study:In this study, the micronucleus rate was counted and the corresponding dose-effectiveness curve was constructed. By F test, the regression coefficient of the rate of micronuclear cells and the dose are statistically significantly (P<0.001). The curve fitting exponents are0.9827、0.9948and0.9952respectively. Statistical analysis shows that relative biological effectiveness (RBE) values of micronucleus rate which induced by different types of radiation and different energies radiation, were not the same value, especially on chronic low doses of ionizing radiation. When the CB micronucleus rate was taken as end point target to research biological dose, the type and energy of radial must be considered simultaneously. In addition, the micronucleus rate and the cumulative dose of the medical radiation workers are higher than the matched controls (P<0.01). This research shows signs of some significant correlations between age, work category and micronucleus rate, cumulative dose (P=0.000). Therefore, the occupational small dose of ionizing radiation has damages on the genetic material of medical radiation workers, and it’s feasible to use lymphocyte micronucleus rate as the radiation contact biomarker of occupational exposure group.We measured GPA mutation frequency in peripheral erythrocytes from the medical radiation workers who are working in the department of Radiology of different hospitals of shanghai. In terms of the GPA mutation frequency, medical radiation workers showed higher mutation frequency than matched controls (P<0.01). The GPA NO and GPA NN and GPA (NO+NN) mutation frequency of the medical radiation workers are30.30±1.80(×10-6) and12.94±2.68(×10-6) and48.72±1.78(×10-6), respectively. And the GPANO mutation of the matched controls frequency is9.53±1.84(×10-6), and the GPA NN and GPA (NO+NN) mutation frequency are9.76±2.02(×10-6) and21.63±1.44(×10-6), separately.The correlations between GPA mutation frequency and age, length of service, micronucleus rate, cumulative dose are significant (P<0.05), especially, age, length of service, micronucleus rate, cumulative dose are most important factors which affect GPA mutation frequency. The GPA mutation frequency goes up with the increasing of cumulative dose, and significant correlation was found between GPA mutation frequency and cumulative dose. The dose-effect relationship curve between GPA mutation frequency and total cumlative dose was constructed. The curve fitting exponents are0.247,0.211and0.316, respectively. It has been proven that GPA gene mutation frequency can be the biological marker of the cumulative effects and the indicator of predicting the risk of tumor induced by ionizing radiation. However, some of the less important factors are neglected. Therefore, making more comprehensive multiple factors analysis is of top importance in order to improve the accuracy of estimating cumulative dose and of forecasting cancer risk by using GPA mutation frequency.Individual radiosensitivity is one of the most important factors which affect GPA mutation frequency. The correlation coefficient of CBMN+3AB index and GPA NO gene mutation frequency is-0.229(P<0.05), but the correlation between GPA NN gene mutation frequency and CBMN+3AB index is not significant. It demonstrates that the stronger of radiosensitivity, the weaker of DNA damage repair ability, and the higher of GPA NO mutation frequency. The result of this study proved that individual radiosensitivity has the obvious influence to the GPANO gene mutation frequency, but the GPANN gene mutation frequency more reflections increase the age change.In addition, average annual radiation doses and GPANO mutation frequency of medical radiation workers who engage in the radiological diagnosis and treatment are significantly higher than the general group and the computed tomograpgy (CT) group. Therefore, we should focus on their future biological effects of radiation and possible risk of getting cancer.