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Cancer risk from professional exposure in staff working in cardiac catheterization laboratory: Insights from the National Research Council's Biological Effects of Ionizing Radiation VII Report

Organisms are affected by different DNA damaging agents naturally present in the environment or released as a result of human activity. Many defense mechanisms have evolved in organisms to minimize genotoxic damage. One of them is induced radioresistance or adaptive response. The adaptive response could be considered as a nonspecific phenomenon in which exposure to minimal stress could result in increased resistance to higher levels of the same or to other types of stress some hours later. A better understanding of the molecular mechanism underlying the adaptive response may lead to an improvement of cancer treatment, risk assessment and risk management strategies, radiation protection, e.g. of astronauts during long-term space flights. In this mini-review we discuss some open questions and the probable underlying mechanisms involved in adaptive response: the transcription of many genes and the activation of numerous signaling pathways that trigger cell defenses - DNA repair systems, induction of proteins synthesis, enhanced detoxification of free radicals and antioxidant production.

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"Adaptive response" - some underlying mechanisms and open questions

Interventional cardiologists who work in cardiac catheterization laboratories are exposed to low doses of ionizing radiation that could pose a health hazard. DNA damage is considered to be the main initiating event by which radiation damage to cells results in development of cancer and hereditary disease. The aim of the present study was to assess the effects of chronic low-dose X-ray radiation exposure on somatic DNA damage of interventional cardiologists working in high-volume cardiac catheterization laboratories. For this analysis, we used peripheral lymphocytes and the assay for micronuclei (MNs), which is considered to be a reliable biological dosimeter for radiation exposure. We obtained peripheral blood from 62 physicians (mean age+/-se = 40.6+/-1.5 years): 31 interventional cardiologists (group I, exposed) and 31 age- and sex-matched clinical cardiologists (group II, nonexposed). Interventional cardiologists showed higher MN values (group I=20.5+/-1.6 vs. group II=12.8+/-1.3, P=0.001), although some overlap was apparent in the individual subject analysis. A correlation between years of professional activity and MN frequency value was detectable for interventional cardiologists (r=0.428, P=0.02) but not for clinical cardiologists (r=0.253, P=0.17). The results indicated that, overall, interventional cardiologists working in a high-volume catheterization laboratory have higher levels of somatic DNA damage when compared with clinical cardiologists working outside the catheterization laboratory. The amount of this damage varies and is only weakly related to the duration of professional exposure, which suggests that a dominant modulation of the underlying genetic substrate by environmental factors has a role in determining the harm in individual physicians.

Somatic DNA damage in interventional cardiologists: a case-control study.

Technical reports series No. 405, International Atomic Energy Agency, Vienna 2001 127 pp., 16 figures, Publication date: January 2002

A Review of “Cytogenetic Analysis for Radiation Dose Assessment—A Manual”

Interventional cardiologists working in high-volume cardiac catheterization laboratory are exposed to significant occupational radiation risks. Common single-nucleotide polymorphisms (SNPs) in DNA repair genes are thought to modify the effects of low-dose radiation exposure on DNA damage, the main initiating event in the development of cancer and hereditary disease. The aim of this study was to determine the relationship between XRCC1 ( Arg194Trp and Arg399Gln ), OGG1 ( Ser326Cys ), APE1 ( Asp148Glu ) and XRCC3 ( Thr241Met ) SNPs and chromosomal DNA damage. We enrolled 77 subjects: 40 interventional cardiologists (27 male, 41.3 ± 9.4 years and 13 female, 37.8 ± 8.4 years) and 37 clinical cardiologists (26 male, 39.4 ± 9.5 years and 11 female, 35.0 ± 9.8 years) without radiation exposure as the control group. Micronucleus (MN) assay was performed as biomarker of chromosomal DNA damage and an early predictor of cancer. MN frequency was significantly higher in interventional cardiologists than in clinical physicians (19.7 ± 7.8‰ vs. 13.5 ± 6.3‰, p  = 0.0003). Within the exposed group, individuals carrying a XRCC3 Met241 allele had higher frequency than homozygous XRCC3 Thr241 (21.2 ± 7.8‰ vs. 16.6 ± 7.1‰, p  = 0.03). Individuals with two or more risk alleles showed a higher MN frequency when compared to subjects with one or no risk allele (18.4 ± 6.6‰ vs. 14.4 ± 6.1‰, p  = 0.02). An interactive effect was found between smoking, exposure >10 years and the presence of the two or more risk alleles on the MN frequency ( F  = 6.3, p  = 0.02). XRCC3 241Met alleles, particularly in combination with multiple risk alleles of DNA repair genes, contribute to chromosomal DNA damage levels in interventional cardiologists.

Genetic polymorphisms in XRCC1, OGG1, APE1 and XRCC3 DNA repair genes, ionizing radiation exposure and chromosomal DNA damage in interventional cardiologists.

Angiocardiography is an X-ray examination of the blood vessels or chambers of the heart for evaluation of the number and severity of blockages in arteries that supply blood to the heart. Cardiologists and staff members applying these procedures are exposed to high levels of scattered radiation. In the present study we analyzed and followed-up on the cytogenetic effects of X-ray angiography in personnel of laboratories for treatment of cardiovascular disease. According to film dosimeter analysis, personnel received 0.25-15 mSv during the previous year (average of 3 mSv/y), which indicated an exposure below the limit established by the International Commission on Radiological Protection (ICRP). Samples of peripheral blood were collected from cardiologists, nurses and technicians and from a matched control group. The incidence of unstable chromosomal aberrations (dicentrics, acentric fragments, ring chromosomes) and cytokinesis-blocked micronuclei were analyzed. Results show a high frequency of acentric fragments in cardiologists, nurses and technicians compared to controls (P < 0.001). When the exposed groups were compared, a higher percentage of acentric fragments was observed in the nurses and technicians compared to cardiologists (P = 0.004). Six individuals presented with dicentric chromosomes and their equivalent whole-body doses ranged from 0.05 to 0.10 Gy. No correlation was observed between chromosome aberrations and annual effective dose or age of the exposed groups. Although the mean frequency of chromosome aberrations in the male workers was slightly higher than in the females, no significant difference was observed between male and female workers in each group (P = 0.86). The mean number of micronuclei per 1000 binucleated cells was significantly higher in the exposed groups compared with the matched control group (P < 0.001). In a follow-up study, chromosome aberrations in lymphocytes of 23 exposed personnel were analyzed five times during 3 years. Results show that the mean number of acentric fragments decreased gradually during 36 months in those workers who followed the radiation protection guides. The results of this study emphasize the importance of individual biomonitoring, limiting exposure and radiation safety programs.

Cytogenetic monitoring of personnel working in angiocardiography laboratories in Iran hospitals.

Purpose : To report 18 months of cytogenetic follow-up for an Iranian worker accidentally overexposed to 192Ir, the mathematical extrapolation and comparison with clinical data. Material and methods : Unstable chromosome aberrations were measured using conventional cytogenetic tests by French and Iranian biological dosimetry laboratories on five occasions after the exposure. The decrease in dicentrics over time was analysed mathematically. In addition, Dolphin and Qdr extrapolations were applied to the data to check the exposure estimates. FISH determination of translocation yields was performed twice by the French laboratory and the results compared with the Dolphin and Qdr corrected values. Results : Dose estimates based on dicentrics decreased from 3.1 0.4Gy at 5 days after the accident to 0.8 ±0.2Gy at 529 days. This could be fitted by double-exponential regression with an inflexion point between rapid and slow decrease of dicentrics after about 40 days. Dose estimates of 3.4 ±0.4Gy for the Qdr model ...

Mathematical methods in biological dosimetry: the 1996 Iranian accident.

In order to evaluate the cytogenetic effects of low doses of radiation by internal or external exposure to iodine-131, we analysed chromosomal aberrations (CA) in peripheral blood lymphocytes from 34 subjects working in the nuclear medicine departments in Iran. The studied groups consisted of 26 individuals (Group A) who were employed in these centres without any evidence of radiation exposure by physical dosimeters or whole body counting, and 8 workers who were suspected to be exposed chronically to low doses of radiation from iodine-131. The results revealed that the mean frequency of CA in group A was not significantly increased compared with the control group (P = 0.21), while in group B the differences were statistically significant (P < 0.05). Moreover, these cytogenetic findings showed chromosome damage depended on internal or external radiation exposures but did not show its relation to the duration of work.

Reza Gholi Assaei

Papers

Cytogenetic monitoring of personnel working in angiocardiography laboratories in Iran hospitals.

Mathematical methods in biological dosimetry: the 1996 Iranian accident.

Chromosomal aberration analysis in lymphocytes from workers exposed to I-131 in nuclear medicine departments in Iran