Healthcare Workers Exposure to Ionizing Radiation: Oxidative Stress and Antioxidant Response.

BACKGROUND: Ionizing radiation is well known to cause oxidative stress which is responsible for various health hazards. Controlling healthcare workers' exposure and raising attention toward continuous monitoring is the first step for improving both the health of healthcare workers and the quality of patient care, thus decreasing both human and economic costs.
OBJECTIVES: To assess oxidative stress by measuring the level of lipid peroxidation, antioxidants, and measure complete blood count (CBC) among healthcare workers exposed to ionizing radiation.
METHODS: A cross-sectional study conducted at the diagnostic radiology department on 31 healthcare workers exposed to ionizing radiation and a non-exposed group of 31 healthcare workers from outpatient clinics. Malondialdehyde (MDA), superoxide dismutase (SOD), and CBC were measured among both groups.
RESULTS: MDA was significantly higher among the exposed group, while the level of SOD was significantly lower. Red blood cells and hemoglobin were significantly lower among the exposed group. The most significant predictor of oxidative stress was the duration of work.
CONCLUSION: Ionizing radiation exposure induce oxidative stress which has an important role in radiation-related health effects. Anemia was the most common hematological health hazards among the exposed group. Copyright:

INTRODUCTION

Medical X-ray imaging is essential in the diagnosis and management of disease, and with technological advancement and usage of CT-scanners larger amounts of ionizing radiation are emitted raising concerns over radiation-related risks.[1] Today, studies on healthcare workers are on accidental overexposure to ionizing radiation, not on hazards of chronic exposure to low dose ionizing radiation. The radiation dose of workers in the diagnostic radiology department varies between 1 and 50 mSv/year in many parts of the world. The International Commission on Radiological Protection (ICRP) has set dose limits of 20 mSv/year, averaged over any 5-year, for occupational exposure.[2]

Most of the radiation damage occurs because of the radiolysis of water which is the main component of tissues with the production of reactive oxygen species (ROS) and reactive nitrogen species (RNS) that causes oxidative damage to proteins, lipids, and DNA.[3]

A recent study conducted on radiological technicians reported that chronic exposure to a low level of ionizing radiation is a non-avoidable occupational hazard that causes oxidative stress and DNA damage which increase the risk of cancer development depending on the time spent with X-rays, amount of radiation received, and the number of patients handled daily.[4]

The hematopoietic system is highly radiosensitive and the influence of radiation on bone marrow can cause Leukemia and manifest first as anemia, neutropenia, and thrombocytopenia. At low doses, ionizing radiation can stimulate or suppress the immune system.[5]

Biomarkers of oxidative stress are important tools in the assessment of oxidative stress conditions. Malondialdehyde (MDA) is one of the best-studied end-products of Lipid peroxidation which is commonly used as an indicator of ROS-mediated damage to cell membranes.[6] Cells are equipped with a defense system against ROS which includes low molecular weight molecules like glutathione (GSH) and antioxidant enzymes such as superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px).[7] Radiation exposure weakens endogenous antioxidant enzymes, which acts as a part of the first-line defense mechanism to maintain redox balance.[8]

Therefore, the present study was conducted to assess oxidative stress by measuring the level of lipid peroxidation and antioxidants among healthcare workers exposed to ionizing radiation as the damage to the body caused by radiation is dose-related and cumulative, often with a long latency period. Thus, the hazards and level of risk should be identified and managed.

METHODS

Study design and study population

A cross-sectional study was carried out at diagnostic radiology department, Zagazig university hospitals in the period from February 2018 to February 2020 on a group of 31 healthcare workers exposed to ionizing radiation during their work at the department and a non-exposed group of 31 healthcare workers selected from outpatient clinics (clinical pathology department) not exposed to diagnostic ionizing radiation. The sample size was calculated using Epi Info 7 program with test power 80% and CI 95%.

Inclusion criteria

Healthcare workers (Radiologists, technicians, and nurses).

Five years of minimum occupational exposure.

Service workers.

Exclusion criteria

Participants having aplastic anemia.

Participants undergoing chemotherapy.

Participants suffering from chronic autoimmune disorders.

Participants suffering from HIV or HBV.

Smokers.

Both groups were comparable as regards sex, age, residence. The individuals of either group did not receive irradiation for diagnosis or treatment purposes that could affect the results of this study. All participants were asked about their age, sex, occupation, marital status, duration of work.

Laboratory investigations

Blood samples were collected by a trained nurse using sterile syringes. Half of the blood collected into tubes containing potassium Ethylenediaminetetraacetic acid (k-EDTA) for measuring of SOD and lipid peroxide Malondialdehyde (MDA). The other half collected in plain glass tubes containing serum for measuring complete blood count (CBC) to measure the level of WBCs to detect leucopenia (<4.4 × 103/mm3), platelets to detect Thrombocytopenia (<150 × 103/mm3) and measuring Hemoglobin (Hb) level, participants considered anemic when HB < 12 g/dl.

A-Assessment of the blood level of Malondialdehyde (MDA)

Plasma MDA concentrations were measured by high-performance liquid chromatography with fluorometric detection as previously described by Nielsen et al.[9] Normal Values: The reference range of MDA is 10–17 nmol/ml.[10]

B- Assessment of erythrocyte activity of Superoxide dismutase enzyme (SOD)

The level of SOD was measured spectrophotometrically, following the method developed by Kakkar et al.[11] Normal Values: The reference range of SOD is 18–24 u/ml.[12]

Environmental measurement

Evaluation of radiation exposure of exposed group done through film badges wore by workers through their work shift and these films read in the Egyptian Atomic Energy Authority (EAEA). The environmental exposure was measured every 3 months. The annual cumulative effective dose was measured. Occupational exposure limits: 20 mSv per year.[13]

Ethical considerations

The Institutional Review Board (IRB) of the faculty of medicine, Zagazig University approved the study protocol (#4209/18-2-2018). A formal letter from the hospital manager was taken to get their permission to collect data. Informed consent was obtained from all the participants after describing the aim of the study and that the data would be for scientific purposes.

Statistical analysis

The collected data were statistically analyzed using SPSS program version 22.0. Qualitative data were presented as frequencies and percentages, Chi-square (χ2), and Fisher Exact tests were carried out for testing the association. Quantitative data were presented as Mean ± SD and compared using independent i-test. Spearman's rank test was used to test correlations. The test results were considered significant when P value ≤ 0.05. Highly statistically significant P value < 0.01.

RESULTS

Participants were comparable to age, sex, marital status, and duration of work. Mean ± SD of the age of exposed group and control group were (35 ± 6.9 & 36.7 ± 9.5), respectively. Mean ± SD of the duration of work was (12.39 ± 6.16 & 12.29 ± 6.65) respectively [Table 1].

Table 1

Some socio-demographic data among the studied groups

Variable	Exposed group (N = 31)	Control group(N = 31)	χ2	P-value
Sex:	N (%)	N (%)
Male	14 (45.2)	9 (29)	1.7	0.29
Female	17 (54.8)	22 (71)
Marital status:	N (%)	N (%)
Single	5(16.1)	6 (19.4)
Married	22 (71)	16 (51.6)	3.2	0.36
Divorced	2 (6.5)	6 (19.4)
Widow	2 (6.5)	3 (9.7)
Age (years):
Mean ± SD	35 ± 6.9	36.7 ± 9.5	-0.825 (T-test)	0.413
Range	24-55	20-56
Duration of work (years):
Mean ± SD	12.39 ± 6.16	12.29 ± 6.65	0.06	0.95
Range	5-30	3-30	(Mann-Whitney-test)

Environmental exposure to ionizing radiation was measured among exposed group. The annual cumulative effective dose of ionizing radiation exposure ranges from 0.21 to 0.27 with a mean of 0.23 ± 0.02.

MDA was significantly higher (P-value < 0.01) among exposed group compared to control group, while the level of SOD was significantly lower (P-value < 0.01) [Table 2].

Table 2

Level of Malondialdehyde (MDA) & Superoxide Dismutase (SOD) among the studied groups

Biomarkers	Exposed group (N=31)	Control group (N=31)	T-test	P-Value
MDA (nmol/ml):
Mean ± SD	24.72 ± 3.64	14.27 ± 1.34	15.1	0.000
Median	24.3	14.5
Range	19.3-31	11.2-16.4
SOD (U/ml):
Mean ± SD	9.89 ± 4	20.49 ± 2.7	-12.2	0.000
Median	9.9	21.2	(Mann Whitney-test)
Range	14.3-18	14.4-23.3

Red blood cells (RBCs) and hemoglobin were statistically significantly lower among the exposed group compared with control group (P < 0.05) [Table 3].

Table 3

CBC measures among studied groups

Variable	Exposed group (N=31)	Control group (N=31)	T-test	P-Value
WBCs (x103/mm3):
Mean ± SD	7.8 ± 2.58	7.6 ± 2.26	0.26	0.79
Range	3.6-15.2	4.9-11.9
RBCs (x103/mm3):
Mean ± SD	4.6 ± 0.88	5.1 ± 0.5	-2.747	0.009
Range	3.6-5.9	4.1-6.8
HB (g/dl):
Mean ± SD	12.4 ± 1.96	13.6 ± 1.31	-2.6	0.009
Range	10.8-16.7	11.6-15.5
Platelets (x103/mm3):
Mean ± SD	249.15 ± 50.6	269.05 ± 67.9	-1.4	0.17
Range	109-347	183-386

There was a statistically significant difference among studied groups regarding the prevalence of anemia (P < 0.05). Among exposed group, 71% of them were anemic, 9.7% of them had leucopenia, and 3.2% of them had thrombocytopenia [Table 4].

Table 4

Frequency distribution of anemia, leucopenia, and thrombocytopenia among studied groups

Variable	Exposed group (N=31)	Control group (N=31)	χ2	P-Value
Anemia (Hb<12 g/dl):
No	9 (29)	21 (67.7)	9.3	0.005
Yes	22 (71)	10 (32.3)
Leucopenia (<4.4 x103/mm3):
No	28 (90.3)	31 (100)	Fisher	0.24
Yes	3 (9.7)	0
Thrombocytopenia
(<150 x103/mm3):	30 (96.8)	31 (100)
No
Yes	1 (3.2)	0	Fisher	1

Figures 1-3 show that there was a negative correlation between the level of MDA, levels of hemoglobin, and SOD, while there was a positive correlation between the level of SOD and levels of hemoglobin.

Figure 1

Line graph showing a significant negative correlation between the level of Malondialdehyde (MDA) and levels of hemoglobin (Hb) among radiation group (P-value = 0.039)

Figure 3

Line graph showing a significant positive correlation between the level of Superoxide Dismutase (SOD) and levels of hemoglobin (Hb) among radiation group (P-value = 0.04)

Line graph showing a significant negative correlation between the level of Malondialdehyde (MDA) and levels of Superoxide Dismutase (SOD) among radiation group (P-value = 0.000)

Results showed a significant negative correlation between the level of SOD, duration of work, and environmental exposure. A significant negative correlation was also found between the level of hemoglobin, age, and duration of work, while there was a significant positive correlation between the level of MDA, duration of work, and environmental exposure among exposed group [Table 5].

Table 5

Correlation between age, duration of work & environmental exposure and levels of Hemoglobin & Malondialdehyde and Superoxide Dismutase among exposed group

Variable	Hemoglobin (g/dl)		Malondialdehyde (nmol/ml)		Superoxide Dismutase (U/ml)
	P-value	r	P-value	r	P-value	r
Age (years)	-0.91	0.04	0.14	0.41	0.172	0.288
Duration of work (years)	-0.90	0.04	0.88	0.04	-0.95	0.03
Environmental exposure (mSV)	-0.87	0.05	0.89	0.04	-0.90	0.04

The most significant predictor of oxidative stress among exposed group was the duration of work [Table 6].

Table 6

Logistic regression analysis for significant risk factors of oxidative stress and Malondialdehyde levels among exposed group

Independent factors	B	S.E	Wald	O.R (C.I)	P-value
Age	0.79	0.21	2.01	2.03 (1.88-4.64)	0.34
Environmental exposure	1.64	0.49	3.99	2.69 (1.06-2.75)	0.91
Duration of work	0.53	0.79	12.18	1.98 (1.05-4.15)	0.04

DISCUSSION

In this study, we aimed to assess oxidative stress by measuring the level of lipid peroxidation and antioxidants among healthcare workers exposed to ionizing radiation. In this study, we demonstrated that the annual cumulative effective dose of ionizing radiation exposure ranges from 0.21 to 0.27 mSV with a mean of 0.23 ± 0.02 mSV. Our results were supported by Awosan et al.[14] as they found that the level of radiation exposure among participants was low (The cumulative exposure over 4 years was 0.19 mSV with an average annual exposure of 0.0475 mSv). Ibitoye et al.[15] also reported a low level of radiation exposure among Hospital staff.

In contrary to our results, in Nigeria, Ogundare and Balogun[16] found the mean annual radiation exposure of radiation workers was 7.7 mSv in 2001, and these findings were higher than our results.

In our study, among the exposed group, 71% of them were anemic, 9.7% of them had leucopenia, and 3.2% of them had thrombocytopenia. The high prevalence of anemia could be attributed to other factors in addition to radiation such as lifestyle, eating habits and most of the participants were females and affected by pregnancy.

Our results were supported by Mohammed et al.[17] as they revealed that two-thirds of radiographers showed small percentages of leukopenia and thrombocytopenia. Pramila et al.[18] also found that the mean WBCs count of Radiographers was significantly lower than that of controls. Furthermore, Davoudi et al.[19] found a significant reduction in WBCs and platelet count among radiation workers, especially with more than 5 years of experience. In disagreement with our results, El-Zayat[20] conducted a study to assess the health risks for medical radiation workers at Cairo University and found that 25% had mild hypochromic anemia, 16% had mild normocytic normochromic anemia, and 5% had Leucopenia. Regarding Awosan et al.,[14] hematological tests showed that 10.0% and 15.5% of subjects had leucopenia and anemia respectively.

The present study showed that MDA was significantly higher among exposed group compared to control group, however, the level of SOD was significantly lower. El-Benhawy et al.[21] found that oxygen free radicals in workers exposed to radiation were significantly higher compared to non-exposed individuals. Furthermore, Kłucinski et al.,[22] reported that chronic exposure to ionizing radiation at low level and chronic oxidative stress could reduce antioxidant levels in workers. In contrast to our study, other studies reported that Levels of free radicals, MDA, and SOD in radiation-exposed workers were significantly higher than control subjects.[2324]

The current study showed a negative correlation between the level of MDA, hemoglobin, and SOD. Our results were contrary to Ahmad et al.,[25] they found that exposure to radiation increased lipid peroxidation and SOD activity. These findings were reported in radiographers exposed to high level of ionizing radiation as compared to control subjects. Moreover, Fang et al.,[26] reported that MDA and SOD levels were significantly lower in workers exposed to low radiation dose for more than 20 years than those of controls. These results showed a relationship between serum MDA, SOD activities, and the duration of radiation exposure.

CONCLUSION

Healthcare workers had various health hazards related to exposure to diagnostic ionizing radiation. Although the exposure level was within the normal limit, exposure to ionizing radiation induces oxidative stress, which has an important role in radiation-related health effects. Anemia was the most common hematological health hazards among the exposed group. So, periodic in-job training is highly recommended and periodic medical examination of exposed healthcare workers is needed to ensure compliance with safety regulations.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.