Analysis of gene expression in mouse brain regions after exposure to 1.9 GHz radiofrequency fields

Purpose: To assess 1.9?GHz radiofrequency (RF) field exposure on gene expression within a variety of discrete mouse brain regions using whole genome microarray analysis. Materials and methods: Adult male C57BL/6 mice were exposed to 1.9?GHz pulse-modulated or continuous-wave RF fields for 4?h/day for 5 consecutive days at whole body average (WBA) specific absorption rates of 0 (sham), ～0.2 W/kg and ～1.4 W/kg. Total RNA was isolated from the auditory cortex, amygdala, caudate, cerebellum, hippocampus, hypothalamus, and medial prefrontal cortex and differential gene expression was assessed using Illumina MouseWG-6 (v2) BeadChip arrays. Validation of potentially responding genes was conducted by RT-PCR. Results: When analysis of gene expression was conducted within individual brain regions when controlling the false discovery rate (FDR), no differentially expressed genes were identified relative to the sham control. However, it must be noted that most fold changes among groups were observed to be less than 1.5-fold and this study had limited ability to detect such small changes. While some genes were differentially expressed without correction for multiple-comparisons testing, no consistent pattern of response was observed among different RF-exposure levels or among different RF-modulations. Conclusions: The current study provides the most comprehensive analysis of potential gene expression changes in the rodent brain in response to RF field exposure conducted to date. Within the exposure conditions and limitations of this study, no convincing evidence of consistent changes in gene expression was found in response to 1.9?GHz RF field exposure.     

Issues in the control of low‐level radiation exposure*

The carcinogenic risks of exposure to low level ionizing radiation used by the International Commission on Radiation Protection (ICRP) have been challenged as being, at the same time, both too high and too low. This paper explains that the epidemiological evidence will always be limited at low doses, so that understanding the cellular mechanisms of carcinogenesis is increasingly important to assess the biological risks. An analysis is then given of the reasons why the challenges to ICRP, especially about the linear non‐threshold response model, have arisen. As a result of considering the issues, the Main Commission of ICRP is now consulting on a revised, simpler, approach based on an individual oriented philosophy. This represents a potential shift by the Commission from the past emphasis on societal‐oriented criteria. These proposals have been promulgated through the International Radiation Protection Association (IRPA) and an open literature publication was published in the Journal of Radiological Protection ¹ in June 1999. On the basis of comments received and the observations presented at the IRPA 10 Conference, the Commission will begin to develop the outline of the next Recommendations. It is now more than ten years since ICRP distributed, for comment, a draft of what was to become the publication of the 1990 Recommendations. The Commission plans to develop its new Recommendations on a time scale of the next four or five years. In this paper, many of the issues that will need to be addressed in the development of the recommendations will be identified. These issues will cover biological effects, dosimetric quantities and the establishment of those levels of dose at which different protection requirements will be put into place. Concepts of exclusion and exemption will need to be clarified as well as the meaning of how to achieve what the proposal identifies as ‘As Low as Reasonably Practicable’ (ALARP). Finally, the Commission has decided to develop an environmental radiation protection philosophy that will need to be developed as part of the new Recommendations.     

Differences in the kinetics of γ-H2AX fluorescence decay after exposure to low and high LET radiation

Purpose:?In order to obtain more insight into heavy ion tumour therapy, some features of the underlying molecular mechanisms controlling the cellular response to high linear energy transfer (LET) radiation are currently analysed.

Materials and methods:?We analysed the decay of the integrated fluorescence intensity of γ-H2AX (phosphorylated histone H2AX) which is thought to reflect the repair kinetics of radiation-induced DNA double-strand breaks (DSB) using Laser-Scanning-Cytometry. Asynchronous human HeLa cells were irradiated with a single dose of either 1.89 Gy of 55 MeV carbon ions or 5 Gy of 70 kV X-rays.

Results:?Measurements of the γ-H2AX-intensities from 15–60?min resulted in a 16 % decrease for carbon ions and in a 43 % decrease for X-rays. After 21?h, the decrease was 77 % for carbon ions and 85 % for X-rays. The corresponding time-effect relationship was fitted by a bi-exponential function showing a fast and a slow component with identical half-life values for both radiation qualities being 24?±?4?min and 13.9?±?0.7?h, respectively. Apparent differences in the kinetics following high and low LET irradiation could completely be attributed to quantitative differences in their contributions, with the slow component being responsible for 47 % of the repair after exposure to X-rays as compared to 80 % after carbon ion irradiation.

Conclusion:?γ-H2AX loss kinetics follows a bi-exponential decline with two definite decay times independent of LET. The higher contribution of the slow component determined for carbon ion exposure is thought to reflect the increased amount of complex DSB induced by high LET radiation.     

Cellular origin of ionizing radiation‐induced NF‐κB activation in vivo and role of NF‐κB in ionizing radiation‐induced lymphocyte apoptosis

Purpose: To investigate the cellular origin of ionizing radiation (IR)‐induced NF‐κB activation in vivo and the role of NF‐κB in IR‐induced lymphocyte apoptosis.

Materials and methods: NF‐κB activities were analysed by gel shift/supershift assay in isolated murine T‐ and B‐cells, macrophages (M?) and tissues from normal and T‐ and B‐cell‐deficient Rag1 mice with or without exposure to IR. IR‐induced lymphocyte apoptosis was determined by analysis of 3,3′‐dihexyloxacarbocyanine iodide (DiOC₆) uptake, annexin‐V staining and the sub‐G0/1 population, or by TUNEL assay.

Results: The results showed that IR activated NF‐κB in lymphocytes, including both T‐ and B‐cells, but failed to do so in M?. Furthermore, T‐ and B‐cell‐deficient Rag1 mice exposed to IR exhibited a significant reduction in NF‐κB activation as compared with normal mice. Although NF‐κB1 (p50) gene knockout or NF‐κB decoy oligonucleotide treatment specifically inhibited IR‐induced lymphocyte NF‐κB activation, they had no significant effect on IR‐induced lymphocyte apoptosis.

Conclusions: This finding suggests that lymphocytes are the main cellular origin of IR‐induced NF‐κB activation in vivo. However, NF‐κB activation has no significant effect on IR‐induced lymphocyte apoptosis.     

Cancer risks from low dose exposure to ionising radiation – Is the linear no-threshold model still relevant?

A review of current knowledge of the biological consequences of diagnostic radiography is well overdue. Despite the monumental investment of time and effort by epidemiologists and biologists over the last 60 years, the ability of low doses of ionising radiation to cause cancer has not been proven. While there is little doubt that serious stochastic and deterministic consequences exist for moderate to large doses, the appropriateness of extrapolating cancer risks to low doses using the linear no-threshold (LNT) model is debatable. Current epidemiological evidence only has sufficient statistical power to detect excess malignancies above around 100 millisieverts (mSv). The lack of detectable excesses below this level could be due to either insufficient statistical power, or genuine lack of carcinogenic potential. The matter has been further complicated by the discovery of various cellular processes including bystander effects, hypersensitivity and adaptive responses, none of which are well understood. A substantial weight of evidence is required to produce a paradigm shift in radiation protection. At present there is insufficient evidence to allow complete rejection of the LNT model, although it must now be acknowledged that the concept has serious limitations.     

Repeated exposure to low‐level extremely low frequency‐modulated microwaves affects baseline and scopolamine‐modified electroencephalograms in freely moving rats

Purpose: To compare in the electroencephalogram of rats the effects of scopolamine (an acetylcholine receptor antagonist) alone and after repeated exposure to low‐level microwaves modulated at extremely low frequency.

Materials and methods: Averaged frequency spectra (0.5–30?Hz) of the electroencephalogram were studied in freely moving rats with carbon electrodes implanted into the somatosensory cortex. The rats were repeatedly (3 days, 30?min?day^?1) exposed to low‐intensity (?0.3?mW?cm^?2) microwaves (915?MHz, 20‐ms pulse duration), amplitude modulated (square‐wave) at extremely low frequency (4?Hz).

Results: The exposure to extremely low frequency microwaves alone significantly enhanced the fast electroencephalographic rhythms (18–30?Hz). This effect was observed neither in subsequent sham‐exposure experiment nor in radiation‐naïve animals. In the microwave‐exposed rats, scopolamine (0.1?mg?kg^?1, subcutaneously) did not cause a slowing in the electroencephalogram that was shown in non‐exposed rats. A similarity between the scopolamine‐induced electroencephalogram effect in the microwave‐exposed rats and that of physostigmine (enhancing the acetylcholine level in the brain) in radiation‐naïve animals was noted. This paradoxical phenomenon stimulates new experimentation for understanding its mechanism(s).

Conclusions: The data obtained provide additional evidence that repeated low‐level exposure to extremely low frequency microwaves can modify an activity of cholinergic system in the brain.     

Time‐ and dose‐dependent changes of intracellular cytokine and cytokine receptor profile of Ewing tumour subpopulations under the influence of ionizing radiation

Purpose: Cytokines and their corresponding cell surface receptors are involved in intercellular signalling pathways and in the radioresistance of normal and malignant cells. The aim was the characterization of the expression of intracellular cytokines, their receptors and apoptosis‐associated markers under the influence of radiation.

Materials and methods: Two Ewing tumours were characterized in vitro before and 4, 24 and 72?h after radiation with 5 and 10?Gy, and in vivo 4, 6 and 15 days after radiation with 5 and 30?Gy by five parameter flow cytometry. Direct fluorescence‐conjugated antibodies directed against intracellular cytokines (interferon‐gamma, tumour necrosis factor [TNF]‐alpha, interleukin 1) and their receptors (CD119, CD120a, CD121a) were used. Annexin V and 7‐amino‐actinomycin D were used to identify radiation‐induced apoptosis.

Results: Inter‐ and intra‐individual heterogeneities were identified by the expression of cytokine receptors and the intracellular cytokine profile before radiation. Time‐ and dose‐dependent up‐regulation of the cytokines TNF‐alpha and interleukin 1 were found in vitro. In vivo, an up‐regulation of CD120a and CD121a was detectable on tumour cell subpopulations. For interferon‐gamma and CD119, no changes were seen.

Conclusions: The observed radiation‐induced changes of cytokine and receptor profile are an indication for complex intercellular interactions in view of radioresistance‐associated mechanisms between cell populations within one individual tumour. The observed heterogeneous response on radiation might have therapeutic implications for an individualized therapy based on combined radiation and cytokine modulation, defined by flow cytometric characterization of markers potentially informative for radioresistance.     

Genetic susceptibility to thymic lymphomas and K‐ras gene mutation in mice after exposure to X‐rays and N‐ethyl‐N‐nitrosourea

Purpose: Ras activation is one of the major mechanisms for the development of murine thymic lymphomas by radiation and chemical carcinogens. To gain insight into the relationship between genetic susceptibility and ras gene mutation, the frequency and spectrum of ras gene mutation was examined in thymic lymphomas from susceptible and resistant mice.

Materials and methods: K‐ and N‐ras mutations in thymic lymphomas that arose in X‐ray‐irradiated and N‐ethyl‐N‐nitrosourea (ENU)‐treated mice of susceptible C57BL/6, rather resistant C3H and their hybrid B6C3F1 were analysed by polymerase chain reaction‐single‐strand conformation polymorphism and subsequent DNA sequencing.

Results: C57BL/6 exhibited a higher incidence of thymic lymphomas after exposure to X‐rays and ENU than C3H, with B6C3F1 being intermediate. K‐ras gene mutations occurred frequently in the pathogenesis of ENU‐induced thymic lymphomas in susceptible C57BL/6 as opposed to resistant C3H. The ras mutations were more frequent in ENU‐induced thymic lymphomas than X‐ray‐induced thymic lymphomas, and with the latter, there was no clear evidence for strain differences, suggesting that the genetic susceptibility to X‐rays was independent of ras activation. The mutations of K‐ras in thymic lymphomas from C57BL/6 were predominantly GGT to GAT in codon 12, whereas this mutation type was never found in those from C3H. No strain difference was observed in the nucleotide sequence or expression levels of O⁶‐alkylguanine alkyltransferase, indicating that this enzyme did not account for the genetic susceptibility to ras activation.

Conclusions: The results indicate that there is a clear strain and carcinogen dependency of K‐ras mutation and that the frequency of ras mutation might determine the genetic susceptibility to ENU‐induced lymphomagenesis, whereas pathways independent of ras activation might determine the susceptibility to X‐ray‐induced lymphomagenesis.     

Occupational exposure to ionizing radiation has no effect on T‐ and B‐cell total counts or percentages of helper,cytotoxic and activated T‐cell subsets in the peripheral circulation of male radiation workers

Purpose: To investigate changes in immune cell subsets in the peripheral circulation of a male population occupationally exposed to ionizing radiation.

Materials and methods: Peripheral blood samples were taken from 194 male workers with cumulative exposures of >200?mSv (mean exposure 331.5?mSv, mean age 51 years) and from a reference population of 131 male workers with cumulative exposures of <27.5?mSv (mean exposure 13.9?mSv, mean age 47 years). Samples were analysed by flow cytometry for T‐ and B‐cell total counts and for the T‐cell subset percentages of CD4⁺ (helper T‐cells), CD8⁺ (cytotoxic T‐cells) and CD3⁺/HLA‐DR⁺ (activated T‐cells).

Results: Comparison of the >200 and <27.5?mSv exposure groups using linear regression analysis showed no statistically significant differences between the two groups for T‐cell total count, B‐cell total count or for percentages of the T‐cell subsets CD4⁺, CD8⁺ or CD3⁺/HLA‐DR⁺ and CD4⁺:CD8⁺. However, statistically significant increases in both T‐ and B‐cell total counts were observed within the two exposure groups and data pooled from both groups when non‐smokers (never and ex‐smokers) were compared with current smokers. For pooled data T‐cell total count increased in smokers by 35% (p=0.0001) and B‐cell total count increased by 37% (p=0.0004).

Conclusions: No significant immunological effects were observed in male radiation workers with cumulative exposures of >200?mSv when compared with a reference population with cumulative exposures of <27.5?mSv, although highly significant increases in both T‐ and B‐cell total counts were observed in smokers compared with non‐smokers.     

Life span,cancer and non-cancer diseases in mouse exposed to a continuous very low dose of γ-irradiation.

Purpose : To analyse the life-span and pathologies of mice living under a continuous very low-dose γ-irradiation. Material and methods : We exposed 300 C57Bl/6J female mice, 3 weeks old, to 10 cGy year -1 γ-rays while 300 control mice lived in the same room. Irradiation was delivered continuously by thorium nitrate. We kept all the animals until natural death and performed autopsy. Results : No difference was observed in life-span (mean life-span ±SE: 805.2 ±9.62 days for controls and 815 ±9.57 days for irradiated mice), weight curves or food intake. At autopsy, cancer was present in 40.9% of controls and 37.9% of irradiated mice. They were mainly represented by lymphomas (23.7 and 24.9%) and histiocytic sarcomas (12.6 and 8.7%, respectively, for controls and irradiated mice). Vascular diseases occurred in 24.1% of controls and 23% of irradiated mice. Infections were present at autopsy in 14.1 and 12.3%, respectively, of controls and irradiated animals. No statistical difference was observed at the end of the experiment for cancer or non-cancer diseases between the two groups. Conclusion : Continuous 10 cGy year -1 γ-irradiation had no adverse effect on malignant or non-malignant diseases in this strain of mouse.     

Lack of inverse dose‐rate effect and binding of the retinoblastoma gene product in the nucleus of human cancer T‐47D cells arrested in G2 by ionizing radiation

Purpose: To investigate the radiosensitivity of human breast cancer cells, T‐47D, irradiated with low dose‐rates and to study activation of the retinoblastoma gene product in the G1 and G2 phases during irradiation.

Materials and methods: Cells were irradiated with ⁶⁰Co γ‐rays with dose‐rates of 0.37 and 0.94?Gy?h^?1. Cell survival was measured as the ability of cells to form colonies. Cells were extracted, fixed and stained for simultaneous measurements of nuclear‐bound pRB content and DNA content. Cell nuclei were stained with monoclonal antibody PMG3‐245 and Hoechst 33258 was used for additional staining of DNA. Two‐parametric flow cytometry measurements of pRB and DNA content were performed using a FACSTAR^PLUS flow cytometer.

Results: It was observed that irradiated cells were arrested in G2. No increase in radiation sensitivity was observed when the cells accumulated in G2. Irradiation of cells at both 0.37 and 0.94?Gy?h^?1 resulted in exponential dose–survival curves with nearly equal α values, i.e. the same radiosensitivity. However, the retinoblastoma gene product was bound in the nucleus, i.e. hypophosphorylated, in about 15% of the cells arrested in G2.

Conclusions: T47‐D cells accumulate in G2 during low dose irradiation, but no inverse dose‐rate effect, i.e. a more efficient inactivation of cells at lower than at higher dose‐rates, was observed. A population of arrested G2 cells has pRB protein bound in the nucleus, and pRB therefore could play a role in protecting cells against radiation‐induced cell death in G2.     

Low‐dose radiotherapy (LD‐RT) and the modulation of iNOS expression in adjuvant‐induced arthritis in rats

Purpose: Low‐dose radiotherapy (LD‐RT) of arthritic joints applied during the peak of the acute inflammatory response improves the clinical and histomorphological development of adjuvant arthritis. The study was undertaken to investigate the cellular composition of the inflammatory infiltrate and the expression of the pro‐inflammatory and anti‐inflammatory enzymes, inducible nitric oxide synthase (iNOS), cyclo‐oxygenase 2 (COX‐2) and haem‐oxygenase 1 (HO‐1), in response to LD‐RT.

Materials and methods: Adjuvant arthritis in female Lewis rats was induced by intradermal injection of heat‐inactivated mycobacterium tuberculosis on day 0. Both arthritic hind paws were sham irradiated (group 1) or X‐irradiated with either 5×1.0?Gy (group 2) or 5×0.5?Gy (group 3) from days 15 to 19 after induction (15 animals/group). On days 21 (n=12 joints/group) and 30 (n=18 joints/group), cryostat sections were analysed histologically and immunohistologically after specific staining for macrophages, iNOS, COX‐2 and HO‐1.

Results: A total of 5×1.0?Gy or 5×0.5?Gy led to a significant reduction of clinical symptoms from days 21 to 29, and a highly significant reduction of cartilage and bone destruction on day 30. Macrophage‐positive areas could be detected continuously throughout the periarticular infiltrate, and were slightly reduced after LD‐RT on days 21 and 30. This reduction was more pronounced after 5×1.0?Gy. Following LD‐RT, the iNOS score was reduced by about 45–50% on days 21 (p<0.05) and 30 (p<0.001). In contrast, the HO‐1 score was increased by about 50% on days 21 (p=0.08) and 30 (p=0.03).

Conclusions: The clinically and histologically observed prevention of the pro‐gression of adjuvant arthritis after LD‐RT given during the peak of the acute inflam‐matory response and the reduction of cartilage and bone destruction in the chronic phase appears to be related to the modulation of iNOS activity by low X‐ray doses.     

Measurement of radiation exposure to household contacts of patients with Graves’ disease treated with low dose radioactive iodine (131I) on outpatient basis

Background

Patients with Graves’ disease (GD) treated with ¹³¹I represent potential radiation hazard to others including household contacts. Radiation safety is considered an integral part in the protocol of this therapeutic modality. Each center offering this medical service gives specific protective recommendations that should help to ensure compliance with guidelines and radiation precaution regulations for each country, with a final aim of reducing potential harmful radiation exposure to others.

Lovastatin causes sensitization of HeLa cells to ionizing radiation‐induced apoptosis by the abrogation of G2 blockage

Purpose: To investigate the effect of inhibition of Ras/Rho‐regulated signalling by 3‐hydroxy‐3‐methylglutaryl coenzyme A (HMG‐CoA) reductase inhibitors (statins) on radiation‐induced cell killing and apoptosis.

Materials and methods: Different human cell lines were pretreated or not with lovastatin before exposure to γ‐rays. Afterwards, radiation‐induced cell killing, formation and repair of double‐strand breaks, activation of radiation‐inducible signal mechanisms (i.e. p53, p21, extracellular‐signal‐related kinase (ERK), NF‐κB), changes in cell cycle progression and apoptosis were analysed.

Results: As shown by a colony formation assay, lovastatin sensitized HeLa cells to γ‐radiation‐induced cell killing. The lovastatin effect was cell‐type specific. Neither the level of γ‐ray‐induced double‐strand breaks nor its repair were affected by lovastatin. Sensitization was independent of p53/p21^Waf1‐ and NF‐κB‐related mechanisms. Radiation‐stimulated activation of ERKs was attenuated by lovastatin. Cell cycle analyses revealed that the level of γ‐ray‐induced G2 blockage was not affected by lovastatin. However, as analysed up to 72?h after irradiation, lovastatin pretreated cells showed an accelerated abrogation of G2 blockage as compared with the control. G2 abrogation is paralleled by an increase in the frequency of apoptotic and necrotic cells.

Conclusions: The data show that lovastatin can render human cells more sensitive to the cytotoxic effect of γ‐rays. This is related to abrogation of G2 blockage and a concomitant increase in apoptotic/necrotic cell death.     

Protein-expression profiles in mouse blood-plasma following acute whole-body exposure to 137Cs γ rays

Purpose: To compare the pattern of protein-expression profiles in blood-plasma after exposure of CBA/CaJ mice to 0 or 3 Gy of ¹³⁷Cs gamma rays.

Materials and methods: Two-dimensional electrophoresis gel coupled with mass spectrometry was used to analyze blood-samples collected at days 2 and 7 post-irradiation. At each sacrifice-time, alterations in expression-level of protein spots between control- and exposed-groups were analyzed statistically by the PDQuest software using Student's t-test (at the significance level of p < 0.05). Mass spectrometry was used to identify the identity of protein-spots with significantly altered expression-level.

Results: At day 2, 18 proteins were significantly up-regulated in exposed-mice. These included: alpha-2-Heremans-Schmid (HS)-glycoprotein, apolipoprotein (Apo)-AII-precursor, Apo-E, beta-2-glycoprotein-I, clusterin, fibrinogen-alpha-chain, fibrinogen-gamma-polypeptide, fetuin-B, haptoglobin, high-molecular-weight (HMW)-kininogen (Kng), low-MW-Kng, Kng1-precursor, liver-carboxylesterase-I-precursor, major-urinary-protein-6-precursor, mannose-binding-protein-C-precursor, mannose-binding-lectin-C, and prothrombin-precursor. Gelsolin was detected in control-mice only. At day 7, high expression-levels of 14 proteins were detected in control-mice (i.e., alpha-1-antitrypsin-precursor, carboxylesterase-N, cholesterol-7-alpha-hydroxylase, contraspin, coagulation-factor-II, coagulation-factor-XIII, gelsolin, immunoglobulin-G-heavy-chain, neurexin, prothrombin-precursor, protein-phosphatase, putative-calcium-influx-channel, vitamin-D-binding-protein, and 1110018G07Rik); while 15 proteins were highly expressed in exposed-mice. These included: alpha-1-acid-glycoprotein, alpha-2-HS-glycoprotein, alpha-1-protease-inhibitor-2, ApoA-IV, ApoC-I, ApoH, beta-1-globin, clusterin, complement-component-3, fibrinogen-beta-chain, HMW-Kng, major-histocompatibility-complex-class-Ia-H2-K, serine-(cysteine)-proteinase-inhibitor, retinoblastoma-associated-protein-140, and vascular-cell-adhesion-molecule-1.

Conclusion: Although different proteins (mostly involved in inflammatory responses) were detected in exposed-mice, alterations in expression-levels of clusterin, gelsolin, kininogen, and alpha-2-HS-glycoproteins were found at both times. Despite the need for validation, the results suggested that alterations in expression-levels of specific proteins may be indicative of radiation-exposure. The results also provided the important step in an eventual establishment of blood-based biomarkers of radiation-exposure in vivo.     

Oxidative stress and glutathione S-transferase genetic polymorphisms in medical staff professionally exposed to ionizing radiation

Purpose: Ionizing radiation (IR) is considered as a diagnostic and therapeutic tool in medicine. However, chronic occupational exposure of medical staff to IR may affect the antioxidant status and, as a result, DNA damage and cancers as well. The objective of our study was to evaluate the oxidative stress profile caused by IR in 29 Tunisian medical staff from radiology and radiotherapy departments, and to find an association between the GSTM1 null, GSTT1 null, and GSTP1 Ile105Val polymorphisms and oxidative stress biomarkers.

Materials and methods: The oxidant biomarkers malondialdehyde (MDA) and advanced oxidation protein product (AOPP) and the activities of the antioxidant superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT) enzymes were spectrophotometrically determined in erythrocytes hemolysates. The analysis of GSTT1 null, GSTM1 null, and GSTP1 Ile105Val polymorphisms was determined for each participant using PCR methods.

Results: A significant increase of white blood cell (WBC) numbers (p?<?.05) and a significant decrease by 11% of hemoglobin (Hb) (p?<?.01) were noted in the exposed subjects in our study. Moreover, we report a significant increase of MDA level and the activities of SOD and CAT enzymes of the IR-exposed group compared to controls (p?<?.001). Interestingly, a close association was noted between the genotypes GSTP1 low active, GSTT1 null, GSTM1 null, and both GSTT1/GSTM1 null and oxidative stress biomarkers, especially with MDA level, SOD, and CAT activities.

Conclusions: Our findings indicate that the medical staff exposed to low IR levels were under risk of significant oxidative stress that was enhanced by their glutathione S-transferase (GST) polymorphisms.     

Chronic low dose UV exposure and p53 mutation: Tilting the odds in early epidermal preneoplasia?

Abstract

Purpose: This review addresses how mutation of the TP53 gene (p53) and ultraviolet light alter the behavior of normal progenitor cells in early epidermal preneoplasia.

Conclusions: Cancer is thought to evolve from single mutant cells, which expand into clones and ultimately into tumors. While the mutations in malignant lesions have been studied intensively, less is known about the earliest stages of preneoplasia, and how environmental factors may contribute to drive expansion of mutant cell clones. Here we review the evidence that ultraviolet radiation not only creates new mutations but drives the exponential growth of the numerous p53 mutant clones found in chronically exposed epidermis. Published data is reconciled with a new paradigm of epidermal homeostasis which gives insights into the behavior of mutant cells. We also consider the reasons why so few mutant cells progress into tumors and discuss the implications of these findings for cancer prevention.