CC BY
0
THE INFLUENCE OF RADIOTHERAPY EXPOSURE ON anti-TPO Ab, anti-Tg Ab, anti-nuclear Ab, anti-DSA Ab AND COMPLETE BLOOD MARKERS IN HOSPITAL PHYSICIAN WORKERS IN NUCLEAR BAGHDAD HOSPITAL
R.A. Mohammed1, Z.Th.Sh. AL-Asady2, M.J. Frayyeh3, B.A.L. AlRubaif
1 Tikrit University, College of Science, Department of Biology, Tikrit, Iraq;
2 Department of Microbiology, College of Science, AL-Karkh University of Science, Baghdad, Iraq;
3 Ministry of Education, Rusafa Directorate of Education I, Aswar High School, Baghdad, Iraq;
4 Department of Biology, College of Science, University of Baghdad, Baghdad, Iraq.
* Corresponding author: bahaa.abdullah@sc.uobaghdad.edu.iq
Abstract. Ionising radiation from radiotherapy can cause thyroid disease, autoimmune antibodies, and haematological invasion. Ionising radiation affects the immune system, and surpassing the body's tolerance can damage the hematopoi-etic system, causing early symptoms and serious consequences. The study used ELISA technique to determine autoan-tibodies and thyroid hormones in whole blood samples from Iraqi physician in Baghdad city for nuclear medicine which exposed daily to radiotherapy according to their routine job. CBC were also determined using autoanalyzer. A group of healthy control patients was also studied. Blood samples from Iraqi doctors who were routinely exposed to radiation were examined, a statistically significant decrease (P < 0.01) in the serum levels of the Triiodothyronine (T3) and Thyroxine 4 (T4) and a statistically significant elevation (P < 0.01) of Anti-Thyroid peroxidase Ab (Anti-TPO Ab), Anti-Thyroglobulin Ab (anti-Tg Ab), and antinuclear antibody (ANA) serum levels in female were seen in contrast to the healthy control group. Compared to healthy controls, female workers had less RBCs and Hb. For that, it can be concluded that the exposure to radiotherapy is effective in female more than male workers in Baghdad city for nuclear medicine which can be due to the effect of radiation low dose on female autoimmune system.
Keywords: Triiodothyronine, Thyroxine 4, Anti-Thyroid peroxidase, Anti-Thyroglobulin Ab, antinuclear antibody.
List of Abbreviations
T3 - Triiodothyronine
T4 - Thyroxine 4
Anti-TPOAb - Anti-Thyroid peroxidase Ab
Anti-Tg Ab - Anti-Thyroglobulin Ab
ANA - antinuclear antibody
Introduction
Radiation is widely recognized as the environmental exposure that has been extensively studied and associated with various effects on the thyroid gland. The primary thyroid manifestation resulting from exposure to radiation is hypofunction, which occurs due to the direct destruction of the thyroid gland. However, it is worth noting that the stimulation of thyroid au-toantibodies can also contribute to the development of both hypothyroidism and hyperthyroidism, as indicated by alterations in thyroid hormone levels. There is evidence suggesting a correlation between autoimmune thyroid disorders (AITDs) and both therapeutic medical ra-
diation and environmental radiation exposure (Agate et al., 2008(. The establishment of radiation protection standards, including dosage limitations, has been undertaken by the International Commission on Radiological Protection (ICRP) (Hafez et al., 2005). According to the relevant literature, the upper limit for the maximum annual allowed dose is 20 mSv for the entire body, 150 mSv for the thyroid or eyes, and 500 mSv for the hands (Kesavachandran et al, 2012). Exposure to radiation can have detrimental consequences on several tissues within the human body. The thyroid gland is recognized as a susceptible organ for radiation-induced harm, mostly due to its anatomical location, which results in significant exposure to scattered irradiation (Farahat et al., 2017). The correlation between exposure to thyroid irradiation and a heightened susceptibility to thyroid neoplasia has been firmly established. Insufficient emphasis has been placed on investigating the potential ramifications of radiation ex-
posure in relation to the heightened susceptibility to autoimmune thyroid disease (AITD) (Bufalo et al., 2011). Autoimmune thyroid illnesses are commonly characterized by the coexistence of TPO-Ab, Tg-Ab, and TSHR-Ab (Fröhlich & Wahl, 2017). Furthermore, the presence of antinuclear antibodies and double strand antibodies, which target the thyroid gland and cause tissue destruction, is also observed (Khalaf et al., 2020). The enzyme thyroid peroxidase is characterized by inadequate glycosylation and is found attached to the cell membrane. It plays a crucial role in the oxidation of iodine (I2) and the subsequent io-dination of tyrosyl residues inside the thy-roglobulin (Tg) molecule. Thyroglobulin is a glycoprotein of considerable size, measuring approximately 600 kilodaltons. It is composed of dimers and typically contains an average of
2 to 3 molecules of thyroxine (T4) along with
3 molecules of triiodothyronine (T3). The molecule exhibits heterogeneity in terms of hormone content, glycosylation, and size (Marcocci & Marino, 2005). The generation of antibodies against thyroglobulin (Tg) can be stimulated through extensive damage of the thyroid gland. However, it is important to note that elevated levels of Tg in the bloodstream alone do not inherently trigger the formation of antibodies (Marcocci & Marino, 2005). Antinuclear antibodies are widely acknowledged as a good diagnostic marker for the assessment of systemic autoimmune disorders. A correlation has been observed between the presence of antinuclear antibodies (ANA) and thyroid antibody positivity in individuals without a diagnosed autoimmune disorder. However, this relationship has not been formally investigated in the juvenile population, as shown in previous studies (Siriwardhane et al., 2018). Various subclasses of double stranded DNA antibodies exist, such as IgA, IgE, IgG, and IgM. The double stranded DNA antibody is derived from nuclear antigens, specifically dsDNA, which are sequestered inside the nucleus and mitochondria and are susceptible to rapid degradation by DNases in the cytoplasm and endosomes (Mis-try & Kaplan, 2017). The primary objectives of this study are to assess the effects of regular ra-
diation exposure on the immune system of male and female healthcare workers at the Baghdad Hospital for Nuclear Medicine.
Materials and Methods
The study started with a group of physician and control volunteers divided into two subgroups: healthy individuals and hospital technicians. Blood samples were taken from January to July 2023 at the Baghdad Centre for Radiotherapy and Nuclear Medicine. The study included a control group of healthy people (control -ve) and technician workers (control +ve). Male and female volunteers aged 20-71 were in the sample. Historical events were documented using survey data.
Blood sampling
Both workers and healthy controls gave 4 ml blood samples. Gel tubes with 3 ml of blood were incubated at 37°C for 30 minutes. The tubes were centrifuged at 3000 RPM for 5 minutes to obtain serum samples for immuno-logical and hormonal testing.
Determination of serum total triiodothyronine (TT3) level
This study measured serum TT3 levels in patients and controls using the Total Triiodothyronine (TT3) ELISA kit. References (Roller et al., 1982; Asaad, 2011) were used to determine this parameter. The microplate wells permitted triplicate testing of serum reference, control, and patient samples. Discarded microwell strips were wrapped in an aluminium bag and stored at 2-8 °C. 50 pl aliquots of standards, control samples, and specimens were carefully placed in designated wells in this experiment. Then, 50 pl of the T3-enzyme conjugate solution and TT3-Antibody-Biotin solution were added to each well, using the same technique. The components were mixed by gently swirling the microplate for 20-30 seconds. Covered, it was incubated for one hour at 25 °C, room temperature. Extract each well contents and rinse three times with 300 pl of washing buffer (1X). To each well, 100 pl of TMB substrate solution was added. Sealed, the plate put in an ambient temperature incubator for 15 minutes. After the
incubation period, 50 pl of stop solution was added to each well and swirled for 15-20 seconds. Each well's 450 nm absorbance was measured with an ELISA reader 5 minutes after the stop solution was added.
This research aims to measure serum total thyroxine
The patients and controls' serum thyroxine (TT4) levels were measured using the Total Thyroxine Enzyme-Linked Immunosorbent Assay (ELISA) kit. This parameter was calculated using the reference (Walker et al., 2013) he microplate wells permitted triplicate testing of serum reference, control, and patient samples. Microwell strips that were not utilised were placed in an aluminium bag and stored at 2-8 °C. With a pipette, 25 pl aliquots of standards, control, or specimen were carefully transferred to their assigned wells. Each well received 50 pl of the working TT4-enzyme conjugate solution, followed by 50 pl of the TT4-Antibody-Biotin solution. To homogenise the contents, the microplate was gently swirled for 20-30 seconds. The microplate was covered and incubated at 25 °C for an hour. Extract each well, wash three times with 30 ml of 1X washing buffer, and add 100 ml of TMB (3,3',5,5'-Tetramethylbenzidine) solution. The plate was sealed and incubated at room temperature for 15 minutes. Then, 50 pl of stop solution was added to each well and gently stirred for 15-20 seconds. Each well's 450 nm absorbance was measured with an ELISA reader 5 minutes after the stop solution was added.
The determination of Thyroid Stimulating Hormone (TSH) level
TSH levels in study participants were measured using a TSH-specific ELISA kit. Cases and controls were studied. The reference (13), which determined this parameter, was followed. A precise arrangement of microplate wells accommodated duplicate assays of serum reference, control, and patient samples. Discarded microwell strips were wrapped in an aluminium bag and stored at 2-8 °C. This experiment involved carefully transferring 50 pl ali-quots of standards, control, or specimen into
designated wells. Next, 50 pl of TSH-enzyme conjugate and TSH-Antibody-Biotin solutions were added to each well. The components were fully mixed by gently swirling the microplate for 20-30 seconds. The microplate was covered and incubated at 25 °C for an hour.
4. Extract each well contents and rinse three times with 300 pl of washing buffer (1X). To each well, 100 pl of TMB substrate solution was added. Sealed, the plate put in an ambient temperature incubator for 15 minutes. After the incubation period, 50 pl of stop solution was added to each well and swirled for 15-20 seconds. Each well's 450 nm absorbance was measured with an ELISA reader 5 minutes after the stop solution was added. Serum samples from patients and controls were examined to determine if immunological biomarkers and hyperthyroidism are related.
Determination of serum thyroid peroxidase antibody level
TPO-Ab was tested in all patients and controls using a proprietary ELISA kit. Biomarker quantification followed (Degroot, 1990). ELISA holder strips are coated. This method produced negative, positive, and calibrator controls. The test samples were diluted at a 1:20 volumetric ratio by gently mixing 10pl sample with 200 pl diluent.100 pl aliquots of diluted sera, calibrator, and controls were carefully put in wells. In well 1A, 100 pl of sample diluent was added to blank the reagent. Gentle tapping removed air bubbles and blended liquid. After that, the mixture incubated at room temperature for 20 minutes. Following extraction, each well was washed three times with 300 pl of washing buffer (1X). Add 100 pl of enzyme conjugate to each well and incubate for 20 minutes at room temperature. Step 5. Repeat. Distribute 100 pl TMB solution and incubate at room temperature for 10 minutes. Next, 100 pl of stop solution was added. In 5 minutes after injecting the stop solution, an ELISA reader evaluated each well's 450 nm absorbance. This investigation measures serum thyroglobulin antibodies. The patients and controls were tested for serum thy-roglobulin antibodies with an ELISA kit. Quantify biomarker after (Wild, 1994). ELISA
holder strips are coated. This method created negative, positive, and calibrator controls. The test samples were diluted by gently mixing 10 pl with 200 pl of sample diluent at a 1:20 ratio. Correctly inserted 100 pl aliquots of diluted sera, calibrator, and controls in wells. In well 1A, 100 pl of sample diluent was added to blank the reagent. Tap liquid containers gently to remove air bubbles. After stirring, the mixture incubated at room temp for 20 minutes. Following extraction, each well was washed three times with 300 pl of washing buffer (1X). Add 100 pl of enzyme conjugate to each well and incubate for 20 minutes at room temperature. Step 5. Repeat. Distribute 100 pl TMB solution and incubate at room temperature for 10 minutes. Next, 100 pl of stop solution was added. In 5 minutes after injecting the stop solution, an ELISA reader evaluated each well's 450 nm absorbance.
Determination the levels of antinuclear antibody
Each study participant's serum antinuclear antibodies were measured using an ELISA kit. This biomarker was measured using reference (Shartt, 1982) protocols. The intended number of coated strips fit in the ELISA holder. In this method, negative, positive, and calibrator controls were constructed. The test samples were diluted at a ratio of 1:20 (volume to volume) by mixing 10 pl of sample with 200 pl of diluent in a gentle manner. Accurately dispersed 100 pl aliquots of diluted sera, calibrator, and controls into their respective wells. To create the reagent blank, 100 pl of sample diluent was added to well 1A. After gently tapping the container to remove air bubbles, the liquid was thoroughly mixed. The mixture was then incubated at room temperature for 20 minutes. Following extraction, each well was rinsed three times with 300 pl of washing buffer (1X). To each well, 100 pl of enzyme conjugate was added and incubated for 20 minutes at room temperature. This was repeated in step 5.
100 pl of TMB solution was distributed and incubated at room temperature for 10 minutes. Next, 100 pl of stop solution was added. After
adding the stop solution, an ELISA reader evaluated each well's 450 nm absorbance within 5 minutes.
Determination of the levels of double strand DNA antibody
To measure serum, a double-stranded DNA antibody ELISA kit was used. Both the patients and controls groups were tested for double-stranded DNA antibodies. This biomarker was measured using reference (Ippolito et al., 2011) criteria. The intended number of coated strips fit in the ELISA holder. This method prepared negative, positive, and calibrator controls. The test samples were diluted at a 1:20 ratio by mixing 10 pl of sample with 200 pl of diluent and gently mixing. 4. 100 pl of diluted sera, calibrator, and controls were added to the wells. To create the reagent blank, 100 pl of sample diluent was added to well 1A. After gently tapping the container to remove air bubbles, the liquid was thoroughly mixed. The mixture was then incubated at room temperature for 20 minutes. All high-quality content was carefully cleaned with three rounds of 300 pl washing buffer (1X) rinse. To each well, 100 pl of enzyme conjugate was added and incubated for 20 minutes at room temperature. To repeat, step 5 was taken. 100 pl of TMB solution was distributed and incubated at room temperature for 10 minutes. Next, 100 pl of stop solution was added. After adding the stop solution, an ELISA reader evaluated each well's 450 nm absorbance within 5 minutes (Conrad et al., 2002)
Statistical analysis
The SAS software was utilized to conduct an analysis of the influence of various factors on the research parameters. The t-test was utilized to evaluate the existence of statistically significant disparities between the means at the significance levels of 0.05 and 0.01.
Ethical approval
The study followed ethical norms. All subjects gave written informed consent before joining the study. The Baghdad Centre for Radiotherapy and Nuclear Medicine authorized the study details.
Results
Demographic distribution Age and gender were used to analyze physician (n = 29) and control (n = 25) demographics (Fig. 1, 2). The results indicate that 72% (21) of the exposed workers were female, whereas 27.5% (8) were male. The control group had 8 men and 17 women. The frequency was likewise higher in women than men. The workers and control also divided according to their age into 15 (51.73%) aged between 20-40 while 13 (52.00%) aged between 40-60 years old. The demographic distribution according to years of services also included, it showed that 14 (48.27%) has less than 5 years while 12
(48.00%) has more than 5 years. Gender was taken in consideration in this study.
Determination of Autoimmune antibodies
Figure 3 shows a significant increase in Anti-Tg Ab, Anti-Tpo Ab and ANA in female physicians exposed to radiotherapy than healthy control, while there is no significant increase in male Anti-Tg Ab, Anti-Tpo Ab and ANA healthy control. It also showed that there is no significant difference in levels of Anti-Tg Ab, Anti-Tpo Ab and ANA in male and female workers. Results showed that there are non-significant differences in the levels of Anti-DSA between exposed workers and healthy control.
25
20
15
10
21
Female Male 20-40 yr. 40-60 yr. More than 5 Less than 5
years years
■ Exposed workers ■ Healthy control
Fig. 1. Distribution of patients and healthy participants based on the gender in this study (n = 54)
0-5
5-20 20-40
Age
40-60
■ Exposed workers ■ Healthy control
Fig. 2. Distribution of patients and healthy participants based on the age in this study (n = 54)
5
0
Results showed that there is a significant decrease in T3 serum level in male and female workers exposed to radiotherapy in their routine day than healthy control. While results showed that there is a significant decrease in serum T4 level in male and female workers than healthy control. While results showed non-significant differences in serum TSH level in physician exposed to radiotherapy (Fig. 4). The results indicated in Figure 5 showed that there is a significant increase in WBC levels in male
and female exposed workers than healthy control. Results showed that there is a significant increase in lymphocyte level in female workers than other group of study male workers and healthy control. But the results indicated in Figures 6, 7, 8 showed that there is a significant decrease in RBC and Hb levels in female workers and female healthy control than male workers and male healthy control, while results showed non-significant differences in platelet levels in all groups of the study.
0,45 0,4 0,35 0,3 0,25 0,2 0,15 0,1 0,05 0
Exposed workers (female) Exposed workers (male) Healthy control (female) Healthy control (male)
■ Anti-TG Ab ■ Anti-TPO Ab ANA
Fig. 3. Determination of autoimmune antibodies in workers exposed to radiotherapy in Baghdad nuclear hospital
30 25 20 15 10 5 0
Exposed workers (female) Exposed workers (male) Healthy control (female) Healthy control (male)
■ T3 BT4 TSH
Fig. 4. Determination of thyroid hormones in workers exposed to radiotherapy in Baghdad nuclear hospital
35 30 25 20 15 10 5 0
Fig. 5. Determination of inflammation biomarkers in workers exposed to radiotherapy in Baghdad nuclear hospital
5,4 5,2 5
4,8 4,6 4,4 4,2 4
Fig. 6. Determination of RBCs in workers exposed to radiotherapy in Baghdad nuclear hospital
16 14 12 10 8 6 4 2 0
Exposed workers Exposed workers Healthy control Healthy control (female) (male) (female) (male)
Fig. 7. Determination of HB in workers exposed to radiotherapy in Baghdad nuclear hospital
Exposed workers Exposed workers Healthy control Healthy control (male) (female) (male) (female)
■ WBC ■ Lymphocyte
RBC
5,2 5,18
4,53 A ACt
■ 4,49
_ _ _ _
Exposed workers Exposed workers Healthy control Healthy control (female) (male) (female) (male)
HB
14,23
14,43
12,33
11,64
Fig. 8. Determination of platelets in workers exposed to radiotherapy in Baghdad nuclear hospital
Platelet
270,06 272 266,21
■
233,25
Exposed workers Exposed workers Healthy control Healthy control (female) (male) (female) (male)
Discussion
Healthcare workers are monitored and limited to 100 mSv every five years. Only 50 mSv is allowed each year. Numerous research investigations have consistently demonstrated that exposure to low-dose ionizing radiation (IR) can give rise to deleterious consequences, encompassing a range of illnesses. Hence, the primary objective of this study was to investigate the impact of low-dose exposure on healthcare professionals employed at a nuclear medicine hospital in Iraq (Wang & Xia, 2019; Watson et al., 1994). According to the data, there is a larger prevalence of hyperthyroidism among women (2%) compared to men (0.02%). Given the presence of a fluctuating and statistically insignificant link between age and years of study (22), our study aimed to examine the role of gender as a determining factor. Gender is widely recognized as a significant demographic characteristic that poses a substantial risk for the development of autoimmune diseases in females. The majority of the entire population under this study consisted of females as women have a higher tendency to acquire gender dys-phoria in comparison to men (19) due to female development, reproduction, and the reproductive hormones, have also been linked to the onset of autoimmune hyperthyroidism (Qashqary et al., 2020; Esfahani et al., 2005).
Our research findings indicate a significant increase in serum Anti-TPO Ab levels among
female workers who have been exposed to radiotherapy. This increase may be associated with lymphocyte infiltration and the stimulation of antibody-dependent cell-mediated cytotoxicity, which is more prevalent in autoimmune diseases (Hasan & Raziq, 2019). This study is similar to Oun (2019), who observed that cleanup workers in Al-Twethata, an area contaminated with low levels of nuclear radiation, exhibited a significant increase in serum levels of anti-thyroid peroxidase antibodies (anti-Tpo Ab) and anti-thyroglobulin antibodies (Anti-Tg Ab) in female workers. Thyroid antibodies serve as biological indicators of thyroid autoimmunity and act as substitutes for eventual thyroid dysfunction. The association between exposure to ionizing radiation and an elevated incidence of thyroid disorders, specifically thyroid cancer, is widely recognized (Abd Oun et al., 2013; Bog-danova & Oleinik, 1995). The prevalence of thyroid cancer is higher among females (Averbeck, 2023).
The study revealed a significant reduction in serum T3 and T4 levels among physicians working in hospitals as a result of their regular exposure to RAI-131, leading to the development of hypothyroidism in these individuals. However, there was no statistically significant increase observed in TSH levels, suggesting that radiation exposure may not have an impact on thyroid stimulating hormone levels in the exposed workers.
The research findings revealed that there was a decrease in T3 and T4 levels among those exposed to radiation, with a drop of -0.015 nmol/L per year and -2.294 nmol/L per year, respectively. There were significant variations in thyroid hormone levels seen between male and female individuals. There was no significant decline in thyroid hormone levels seen as the average effective doses increased (Shan Guo et al., 2021).
Our study also examined the impact of ionizing radiation on CBC in physicians who were exposed to radiotherapy during their routine work. The study indicated a statistically significant elevation in white blood cell (WBC) count and lymphocyte levels among the employees, although a statistically significant drop in red blood cell (RBC) count was observed in all female groups. The study found that cumulative ionizing radiation doses increased the incidence of acute myeloid and acute lymphoblastic leukemia (Li et al., 2018). An investigation demonstrated a correlation between prolonged exposure to low levels of radiation and the death rate in individuals who were regularly checked for radiation levels (Heydarheydari et al., 2016). Additionally, research revealed that exposure to ionizing radiation resulted in an elevated frequency of peripheral blood cells and chromosomal abnormalities, while simultaneously reducing the levels of antioxidants. Consequently, these findings suggest a radiation exposure increase the susceptibility to the formation of cancer.
The increased susceptibility of hematopoi-etic progenitor cells to radiation may be attributed to radiation-induced reductions in bone marrow stem cell factors and elevations in circulating pro-inflammatory factors. Furthermore, it has been observed that (RBC) and (HB) counts exhibit are more sensitive to low-dose ionizing radiation than WBC counts. Nevertheless, our investigation observed a significant drop in the counts of radiologists such as red blood cells (RBC), white blood cells (WBC),
platelets (PLT), and hemoglobin (HB) with the progressive increase in cumulative dose. The study findings indicate that platelet has no statistically significant impact across the groups. In the initial phase, a link was established between the cumulative radiation dosage and platelet (PLT) counts in a cohort of medical radiation workers (Qian et al., 2016). This study found that long-term ionizing radiation exposure increased two blood biomarkers, Il-6 and eosinophil, even at safe doses. As a result, this rise may cause cancer. Research shows that medical supplement users have lower levels of RBC, HGB, HCT, CHCM, and lymphocytes (p = 0.008, p = 0.036, p = 0.02, p = 0.038, p = 0.044) compared to non-users (Bahrami Asl et al., 2023).
Conclusion
The blood cell levels of individuals who are exposed to low-dose radiation in occupational settings are affected. Specifically, the counts of red blood cells (RBCs), platelets (PLTs), and hemoglobin (HB) exhibit varying degrees of change as the cumulative radiation dosage increases. Moreover, it has been observed that the levels of thyroid hormones, white blood cell (WBC) count, and lymphocytes demonstrate diverse alterations in response to escalating amounts of radiation exposure. The present work proposes that hematological indicators have the capacity to function as biomarkers for assessing sensitivity to low-dose ionizing radiation. This suggests that there is a requirement for the establishment of uniform criteria for radiation protection and the improvement of the occupational setting for individuals who encounter ionizing radiation within medical facilities.
Acknowledgment
Thanks to everyone who supported this
study.
Conflict of Interest: no conflicts.
References
ABD OUN M., AL-THWANI A., KHUDAIER S. & KAMEL L. (2013): Thyroid Examination in Low-Radiation Exposed Iraqi Clean-up Workers - Immunogenetic Study. Journal of US-China Medical Science 10(3-4), 85-92.
AGATE L., MARIOTTI S., ELISEI R., MOSSA P., PACINI F. & MOLINARO E. (2008): Thyroid Autoantibodies and Thyroid Function in Subjects Exposed to Chernobyl Fallout during Childhood: Evidence for a Transient Radiation-Induced Elevation of Serum Thyroid Antibodies without an Increase in Thyroid Autoimmune Disease. J Clin Endocrinol Metab 93(7), 2729-36.
ASAAD A. (2011): Evaluation of Anti thyroid Hormones Levels among Iraqi Women Suffering from Multi Recurrent Spontaneous Abortion. Thesis. College of Science. University of Baghdad, Iraq.
AVERBECK D. (2023): Low-Dose Non-Targeted Effects and Mitochondrial Control. International Journal of Molecular Sciences 24(14), 11460.
BAHRAMI ASL F., ISLAMI-SEGINSARA M., EBRAHIMI KALAN M., HEMMATJO R., HESAM M. & SHAFIEI-IRANNEJAD V. (2023): Exposure to ionizing radiations and changes in blood cells and in-terleukin-6 in radiation workers. Environmental Science and Pollution Research 30(13), 35757-68.
BOGDANOVA V.A. & OLEINIK (1995): Thyroid cancer in the Ukraine. Nature 375(1), 365.
BUFALO E., DE NADAI C., BARBIERI B., MARCELLO A., CUNHA L., MORARI C. & WARD S. (2011): Thyroid Disruptors: How They Act and How We React. In: Basic and Clinical Endocrinology Up-to-Date. IntechOpen.
CONRAD K., SCHÖSSLER W., HIEPE F. & FRITZLER M. (2002): Autoantibodies in systemic autoimmune disease. A diagnostic reference. Autoantigens, autoantibodies, autoimmunity. Edi. PABST2, 21.
DEGROOT J. (1990): Hetergeneity of human antibodies to TPO thyroperoxides. Thyroid autoimmunity 207, 177-182.
ESFAHANI F., KAKHKI R. & FALLAHI B. (2005): Comparative evaluation of two fixed doses of 185 and 370 MBq I 131, for the treatment of Graves' disease resistant to antithyroid drugs. Hell JNucl Med 8, 158-161.
FARAHAT A., MANSOUR N., SHETA M., ALRAMLAWY A. & RAMADAN M. (2017): Autoimmune thyroiditis among ionizing radiation exposed workers in cardiac catheterization units. Egyptian Journal of Occupational Medicine 41(1), 127-141.
FRÖHLICH E. & WAHL R. (2017): Thyroid Autoimmunity: Role of Anti-thyroid Antibodies in Thyroid and Extra-Thyroidal Diseases. Front Immunol 8, 521.
HAFEZ A., SMITH M., MATTHEWS J., KALAP G. & SHERMAN P. (2005): Radiation exposure to the hands of orthopaedic surgeons: are we underestimating the risk? Arch Orthop Trauma Surg 125, 330-335.
HASAN R. & RAZIQ A. (2019): Studying the Frequency of Autoimmune Thyroid Diseases in Duhok Province. Science Journal of University of Zakho 7(2), 45-49.
HEYDARHEYDARI S., HAGHPARAST A. & EIVAZI M.T. (2016): A novel biological dosimetry method for monitoring occupational radiation exposure in diagnostic and therapeutic wards: From radiation dosimetry to biological effects. JBiomedPhys Eng 6(1), 21-26.
IPPOLITO A., WALLACE J., GLADMAN D., FORMATIN R., UROWITZ M., WERTH V., COST-NER M., GORDON C., ALARCON S., RAMSEY-GOLDMAN R., MADDISON P., CLARRKE A., BERNATSKY S., MANZI S., MERRILL T., GINZLER E., HANLY G., NIVED O., STURFELT G., SANCHEZ-GUERRERO J., BRUC I., ARANOW C., ISENBERG D., ZORN A., MANGER S., BUYON J., KALUNIAN K., DOOLEY A., STEINSSON G., VOLLENHOVEN F., STOLL T., WEIS-MAN M. & PETRI M. (2011): Autoantibodies in systemic lupus erythematosus: comparison of historical and current assessment of seropositivity. Lupus 20, 250-255.
KESAVACHANDRAN N., HAAMANN F. & NIENHAUS A. (2012): Radiation exposure of eyes, thyroid gland and hands in orthopaedic staff: a systematic review. Eur J Med Res 17(1), 28.
KHALAF Z.A., JASIM H.M., KADAM S.M. & MAHDI A.A. (2020): Thyroid Autoantibodies as a Useful Guideline in Hyperthyroidism Patients Treated with Radioactive Iodine. Systematic Reviews in Pharmacy 11(8).
LI X., CUI W., HULL L., SMITH J.T., KIANG J.G. & XIAO M. (2018): Effects of low-to-moderate doses of gamma radiation on mouse hematopoietic system. Rad Res 190(6), 612-622.
MARCOCCI C. & MARINO M. (2005): Thyroid directed antibodies. In: Werner andIngbar's the thyroid: a fundamental and clinical text 9, pp. 360-372. Lippincott Williams &Wilkins.
MISTRY P. & KAPLAN M.J. (2017): Cell death in the pathogenesis of systemic lupus erythematosus and lupus nephritis. Clinical Immunology 185, 59-73.
QASHQARY M., TOBAIQY M., AL-SUTARI M.M., MUJALLAD A. & ALSHEIKH I. (2020): Prevalence of Suspected Cases of Hyperthyroidism in Jeddah by Using Wayne's Scoring Index. Cureus 12(11), e11538.
QIAN Q.Z., CAO X.K., LIU H.Y. ET AL. (2016): Analysis of hemogram of radiation workers in Tangshan, China. J Clin Lab Anal 30(5), 682-688.
ROLLER E., BUZZIGOLI G. & PLASSIO G. (1982): Diagnosis 13, 892.
SHAN GUO Q., RUAN P., HUANG W.X., HUANG D.Z. & QIU J.C. (2021): Occupational Radiation Exposure and Changes in Thyroid Hormones in a Cohort of Chinese Medical Radiation Workers. Biomedical and Environmental Sciences 34(4), 282-289.
SHARTT W. (1982): An enzyme linked microsomal antibodies 55, 155-1.
SIRIWARDHANE T., KRISHNA K., RANGANATHAN V., JAYARAMAN V., WANG T., BEI K., RA-JASEKARAN J.J. & KRISHNAMURTHY H. (2018): Exploring systemic autoimmunity in thyroid disease subjects. Journal of Immunology Research.
WALKER S., BECKETT G., RAE P. & ASHBY P. (2013): Clinical Biochemistry, 8th Edition. John Wiley and Sons, Ltd.
WANG X. & XIA Y. (2019): Anti-double Stranded DNA Antibodies: Origin, Pathogenicity, and Targeted Therapies. Front Immunol 10, 1667.
WATSON F., PICKERIL P., DAVIES R. & WEETMAN P. (1994): Analysis of cytokine gene expression in Graves' disease and multinodular goiter. J Clin EndocrinolMetab 79, 355-360.
WILD D. (1994): Immunoassay handbook. Stockton, 339 pp.
