Primary Study Of Insulin-like Growth Factor Binding Protein 3(IGFBP-3) As An Indicator Of Occupational Exposure To Ionizing Radiation

ObjectiveIn this study,we analyzed the effects of ionizing radiation on the expression level of IGFBP-3 in human peripheral blood serum and blood cell culture from two aspects of occupational exposed population and in vitro irradiated cell experiment,combined with the population hematological indicators and micronucleus test results,to explore the potential of IGFBP-3 as an indicator of occupational exposure to ionizing radiation.It provides necessary reference for other scholars to evaluate the biological health effects of radiation workers and to establish biological radiation dosimeter at molecular level.MethodsA total of 228 radiological workers(122 males and 106 females)were randomly selected,with a mean age of 37.98±9.29 years.According to different types of radiology,all radiological workers were divided into interventional radiology(n=52),nuclear medicine(n=49),radiotherapy(n=52)and diagnostic radiology(n=75)group.On the basis of informed consent,a questionnaire survey was conducted for the radiation workers,and the personal dose monitoring results were collected and sorted out.5 m L of venous blood from the elbow was extracted,and the serum IGFBP-3level,micronuclei assay(MN)rate and hematological indexes(including WBC,RBC,LY,Hb,PLT)were determined.The venous blood from the elbow of 2 healthy adults(1 male and 1 female)was collected with an EDTA-NA2 anticoagulant tube.The blood samples were divided into six parts.X-ray irradiation with doses of 0Gy,0.25Gy,0.5Gy,1Gy,3Gy and5Gy was received at room temperature,with dose rate of 2Gy/min and irradiation range of 10×10cm~2.The irradiated blood samples were divided into three sections and inoculated in complete medium of RPMI-1640.The samples were cultured at 37℃for 12h,24h and 48h,and then harvested.After harvesting the culture,the supernatant was isolated and the expression level of IGFBP-3 in cell cultures of each group was determined at different time points.The levels of IGFBP-3 in the serum of radiation workers and the supernatant of peripheral blood cell cultures of healthy people were determined by enzyme linked immunosorbent assay.SPSS 25.0 was used for data statistical analysis,P<0.05indicates that the difference is statistically significant(bilateral test).Graphics were drawn using Graphpad7.0 software.Results(1)Personal dose monitoring results:The difference of annual effective dose among the four groups of radiation workers was statistically significant(F=11.769,P<0.05).The annual effective dose of interventional radiology group and nuclear medicine group was higher than that of radiotherapy and diagnostic radiology group,respectively(P<0.05).However,there was no statistically significant difference between the interventional radiology group and the nuclear medicine group,or the diagnostic radiology group and the radiotherapy group.The difference of annual effective dose among different occupational groups was statistically significant(F=10.780,P<0.05),and the annual effective dose of nurse group was higher than physician group and technician group(P<0.05).(2)The level of serum IGFBP-3 in radiological workers and its influencing factors:There was no difference in the level of serum IGFBP-3 in radiological workers of different genders or occupations(P>0.05),but there was a statistically significant difference in IGFBP-3 levels among different types of radiation workers(F=9.071,P<0.05).Serum IGFBP-3 levels in interventional radiologists were significantly higher than that in nuclear medicine,radiotherapy,and diagnostic radiology(P<0.05),but there was no statistically difference in nuclear medicine group,radiotherapy group and diagnostic radiology group(P>0.05).The results of multiple linear regression showed that the level of IGFBP-3 in serum was affected by the type of radiation and annual effective dose(P<0.05),IGFBP-3 level increased gradually with the increase of length of service and annual effective dose.(3)Results of peripheral hematology indicators:the count of WBC,RBC,LY,PLT and Hb concentrations of radiation workers in the four groups were all within the normal range.The LY count in the nuclear medicine group was lower than that of the other three groups(P<0.05);The Hb content in interventional radiology was significantly higher than that in nuclear medicine and diagnostic radiology(P<0.05);The RBC count of nuclear medicine group was lower than that of interventional radiology group and radiotherapy group(P<0.05);There was no statistical significance in the differences of other indicators among all groups(P>0.05).(4)The micronucleus test results of peripheral blood lymphocytes:there was no statistically significant difference in micronucleus rate among different sex groups and different effective dose groups(P>0.05);There were significant differences in micronucleus cell rate and micronucleus rate among different radiation types(P<0.05),and the micronucleus frequency of interventional radiology group was higher than that of other three groups.There was significant difference in micronucleus cell rate and micronucleus rate among different occupations(P<0.05),and it was higher in the physician group than other two groups.There were significant differences in micronucleus cell rate and micronucleus rate among different age groups(P<0.05),and the rate with age≥40 group was higher than that in other two groups.There were significant differences in micronucleus cell rate and micronucleus rate among groups in different length of service(P<0.05),and the rate with length of service≥15 years was higher than that with length of service<5 years.(5)Radiation dose and culture time had no significant effect on the expression of IGFBP-3 in culture supernatant(P>0.05).In the range of 0-3 Gy dose,IGFBP-3level increased gradually with the increase of radiation dose,but there was no statistical significance between different dose groups(P>0.05).When the radiation dose reached 5Gy,the level of IGFBP-3 in serum culture decreased,but there was no statistical significance compared with other dose groups(P>0.05).The dose-effect curve conforms to the quadratic function,and the fitting curve is as follow:Y=-2.79D~2+14.24D+507(R~2=0.876).ConclusionThe level of serum IGFBP-3 expression in peripheral blood of radiological workers may be related to dose of ionizing radiation,and IGFBP-3 level has the potential to be a biomonitoring indicator for long-term chronic low-dose ionizing radiation occupational exposure.In the case of acute high-dose exposure,the feasibility of IGFBP-3 as a biomonitoring indicator of ionizing radiation exposure in human body still needs a further research.