Genetic factors can modify susceptibility to the carcinogenic effect of ionising radiation. To establish if radioiodine-induced thyroid cancer is similarly genetically influenced, we studied F1 hybrid crosses between inbred mouse strains. Mice were perinatally exposed to iodine-131 and thyroid tissues examined after 18 months. Differences in the incidence and distribution of histological subtypes were quantified in relation to genetic background. As expected, the occurrence of thyroid lesions was significantly higher in irradiated mouse hybrids than in unirradiated controls. The most frequent alterations were the simple and the complex hyperplasias, followed by follicular adenoma and, less frequently, follicular carcinoma. Both the incidence and distribution of the histiotype were different between the hybrid mouse crosses. Crosses using JF1 mice (M. m. molossinus) produced F1 offspring that were more resistant to radiation-induced thyroid lesions. Sequence analysis of Braf, Ret, Hras, Kras, Kit and Trp53, all genes that are commonly mutated in human thyroid cancers, did not show any evidence of mutation in the tumours. However, microsatellite analysis of genomic DNA revealed frequent allelic imbalances in complex hyperplasia and follicular adenoma. We conclude that genetic background, in particular the JF1 genotype, confer differences in susceptibility to the carcinogenic effects of radioiodine on the thyroid.
WTF-B, a type of water-soluble homogeneous polysaccharide, was isolated and purified from Tremella Fuciformis. To investigate the radioprotective effect of WTF-B, we employed a 30-day survival assay. Mice were treated with WTF-B once per day for three consecutive days before 8-Gy gamma irradiation. The treatment groups receiving 54 and 72 mg/kg body weight (b.w.) of WTF-B showed 50% survival post-irradiation. The hematological parameters of the peripheral blood indicated that WTF-B, when administered at doses of 72 mg/kg b.w., significantly restored hemoglobin, white blood cell counts and red blood cell counts by the 14th day and 18th day. In addition, spleen colony forming units (CFU-S), the number of nucleated cells in bone marrow (BMNC) and spleen index were used to investigate the radioprotective effect of WTF-B on the hematopoietic system. The treatment groups receiving WTF-B at 18, 54 and 72 mg/kg b.w. doses presented significantly higher BMNC compared to radiation-only group. The group administered 72 mg/kg b.w. WTF-B presented a significant change in CFU-S compared to the radiation-only group. We also completed micronucleus and chromosome aberration assays to explore genotoxicity. The results of those assays indicated that the number of micronuclei induced by 2-Gy irradiation in a group treated with 72 mg/kg b.w. WTF-B decreased from 30.30‰ to 11.32‰. The chromosomal aberration produced by 3-Gy irradiation in the group receiving 72 mg/kg b.w. WTF-B decreased from 56.01% to 28.13%. The results of the present study indicate a potential use for WTF-B as a radioprotector.
This study aims to investigate the efficacy of in vitro Thallium-201 Chloride (Tl-201) and in vitro and in vivo Tc-99m HYNIC-coupled Annexin V (TAV) in the early detection of radiation induced apoptosis, a proxy indicator of radiation therapy (RT) efficacy. In vitro Tl-201 and TAV accumulation and efflux in non-small cell lung cancer were measured post irradiation at 5 different gamma ray doses. The replication rates (RR) of the cell lines were also measured. The same non-small cell lung cancer line was inoculated into the left femur. In vivo non-invasive Tl-201 and TAV tracer biodistribution studies were performed. Cell RR decrease with increased radiation dose was observed 48 hours after irradiation. Apoptotic cell number was found to have increased in response to 9 Gy and 12 Gy radiation dose. Tl-201 accumulation in the 9 Gy and 12 Gy irradiation groups was found to be higher than the lower irradiation groups. Quick Tl-201 efflux was observed in the 9 Gy and 12 Gy irradiated cells. At 48 hours after irradiation with 9 Gy and 12 Gy, Annexin V accumulation was found to be higher than in the control and 3–6 Gy groups. In vivo mouse model confirmed the increased TAV uptake in implanted tumors for relatively high 9 Gy irradiation as compared to non-irradiated controls. TAV may prove to be an effective radiotracer for early assessment of radiation therapy efficacy, via apoptosis, in human lung cancers.
ON 01210.Na (Ex-RAD), a chlorobenzylsulfone derivative was investigated for its pharmacologic and radioprotective properties when administered via oral and subcutaneous (SC) routes. The goals of the study were to assess the comparative bioavailability of ON 01210.Na when administered by oral versus SC routes and to demonstrate that the oral drug delivery of ON 01210.Na afforded survival advantage similar to SC dosing. Pharmacokinetics was studied after two doses, 24 h apart, of ON 01210.Na (500 mg/kg) administered to male C3H/Hen mice (7–9 weeks) via SC injection or oral route. The dose response (100 to 750 mg/kg) and survival advantage of ON 01210.Na administered at 24 h and 15 min prior to 7.5 or 8 Gy whole body irradiation from a 137Cs source (dose rate 1 Gy/min) were studied in these mice. Effects on the hematopoietic system were investigated by complete blood count and granulocyte-macrophage colony forming unit assay. A significant survival advantage and hematopoietic protection were observed after prophylactic oral ON 01210.Na and results were comparable to SC administration. These findings correlated well with pharmacokinetic data. Both SC and oral ON 01210.Na showed significant survival advantage against radiation toxicity and ON 01210.Na mediated hematopoietic protection plays key role in enhanced survival of mice. Oral administration holds better clinical promise as an effective countermeasure not only for early-responders in a nuclear accident, but also for the at-risk civilian population.
This two-generation study evaluated the effects of depleted uranium (DU) on reproduction in rats. Across two generations, Wistar rats (30/sex/group) were maintained on feed containing DU at dose levels of 0 (control group), 4 (DU4 group), or 40 (DU40 group) mg kg–1 day–1 for 4 months prior to mating. After 4 months of exposure, the pregnancy rate, normal labour rate, and survival rate of offspring produced by F1 rats were all significantly decreased as compared to the control group, and especially in the DU40 group, these parameters fell by half to two-thirds, while no adverse effects were evident in F0 rats. The uranium content in the testes and ovaries of F1 rats in the DU4 and DU40 groups was significantly higher than that found in F0 rats. The levels of sex hormone in the serum were disorder in both generations. The enzymes related to spermiogenesis were also significantly different between generations, and the damage was more severe in F1 rats. In conclusion, the reproductive effects in F0 rats were slight after chronic oral exposure to DU, while the effects were obvious in F1 rats.
We examined the effects of prostaglandin E1 (PGE1) on radiation-induced proliferation inhibition and apoptosis in keratinocytes and healing of radiation-induced skin injury in a rat model. PGE1 had a protective effect on radiation-induced growth inhibition in keratinocytes in vitro, but not in fibroblasts. Varying concentrations of PGE1 were subcutaneously administered into the posterior neck region. X-irradiation at a dose of 20 Gy was administrated to the lower part of the back using a lead sheet with two holes 30 min to 1 h before or after the administration of PGE1. Although X-irradiation induced epilation, minor erosions, or skin ulcers in almost all rats, PGE1 administration prior to irradiation reduced these irradiation injuries. Staining with terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling showed that proportions of apoptotic keratinocytes in the X-irradiated skin of PGE1-administered rats were significantly lower than for those in the skin of rats which did not receive PGE1. Cutaneous full-thickness defective wounds were then formed in X-irradiated areas to examine the time course of wound healing. Wound healing was significantly delayed because of X-irradiation, but PGE1 administration prior to irradiation led to a significantly shorter delay in wound healing compared with controls. Decreasing delay in wound healing was correlated with concentration of PGE1 administrated. Thus, PGE1-administration may potentially alleviate the radiation-induced skin injury.
Lydia LASCHINSKY, Michael BAUMANN, Elke BEYREUTHER, Wolfgang ENGHARDT, Malte KALUZA, Leonhard KARSCH, Elisabeth LESSMANN, Doreen NAUMBURGER, Maria NICOLAI, Christian RICHTER, Roland SAUERBREY, Hans-Peter SCHLENVOIGT, Jörg PAWELKE
The notable progress in laser particle acceleration technology promises potential medical application in cancer therapy through compact and cost effective laser devices that are suitable for already existing clinics. Previously, consequences on the radiobiological response by laser driven particle beams characterised by an ultra high peak dose rate have to be investigated. Therefore, tumour and non-malignant cells were irradiated with pulsed laser accelerated electrons at the JETI facility for the comparison with continuous electrons of a conventional therapy LINAC. Dose response curves were measured for the biological endpoints clonogenic survival and residual DNA double strand breaks. The overall results show no significant differences in radiobiological response for in vitro cell experiments between laser accelerated pulsed and clinical used electron beams. These first systematic in vitro cell response studies with precise dosimetry to laser driven electron beams represent a first step toward the long term aim of the application of laser accelerated particles in radiotherapy.
In the 1970s and 1980s, Planel et al. reported that the growth of paramecia was decreased by shielding them from background radiation. In the 1990s, Takizawa et al. found that mouse cells displayed a decreased growth rate under shielded conditions. The purpose of the present study was to confirm that growth is impaired in organisms that have been shielded from background radiation. Radioprotection was produced with a shielding chamber surrounded by a 15 cm thick iron wall and a 10 cm thick paraffin wall that reduced the γ ray and neutron levels in the chamber to 2% and 25% of the background levels, respectively. Although the growth of Paramecium tetraurelia was not impaired by short-term radioprotection (around 10 days), which disagreed with the findings of Planel et al., decreased growth was observed after long-term (40–50 days) radiation shielding. When mouse lymphoma L5178Y cells were incubated inside or outside of the shielding chamber for 7 days, the number of cells present on the 6th and 7th days under the shielding conditions was significantly lower than that present under the non-shielding conditions. These inhibitory effects on cell growth were abrogated by the addition of a 137Cs γ-ray source disk to the chamber. Furthermore, no growth retardation was observed in XRCC4-deficient mouse M10 cells, which display impaired DNA double strand break repair.
The Khewra Salt Mines, the second largest salt mines in the world, are located 160 km south of Islamabad, the capital of Pakistan. Around 1000 workers are involved in the removal of salt from these mines. More than 40,000 visitors come annually to see the mines. The visitors and workers are directly exposed to the internal and external radiological hazards of radon and gamma rays in these mines. The general public is affected by the intake of the salt containing the naturally occurring radionuclides. Therefore the concentration of radon (222Rn) in the Khewra Salt Mines and activity concentrations of the naturally occurring radionuclides in the salt samples from these mines were measured. Both active and passive techniques were employed for the measurement of radon with Radon Alpha Detector (RAD-7) and SSNTD respectively. The concentration of 222Rn was 26 ± 4 Bq m–3 measured by the active method while 43 ± 8 Bq m–3 was measured by the passive method. The activity concentration of the radionuclides was measured using gamma ray spectrometry with HPGe detector. The mean activity of 40K in salt samples was found to be 36 ± 20 Bq kg–1 and the concentration of 226Ra and 232Th in the salt samples was below the detection limits. Gamma radiation hazard was assessed in terms of the external gamma dose from salt slabs and the rooms made of salt and the annual effective dose due to gamma radiation. The exposure to radon daughters, annual effective dose and excessive lifetime cancer risk due to radon in the mines were estimated. The mean annual effective dose due to an intake of 40K from the salt was calculated as 20.0 ± 11.1 μSv, which is lower than the average annual effective dose rate of 0.29 mSv, received by the ingestion of natural radionuclides. Due to the low concentration values of primordial radionuclides in the salt and radon (222Rn) in the mines, a ‘low level activity measurement laboratory' is suggested to be established in these mines.
Osteopontin (OPN) serves as an indicator of resistance to radiotherapy. However, the role of OPN in the development of acquired radioresistance in human lung cancer cells has not yet been fully elucidated. Therefore, the potential importance of OPN as a marker of lung cancer with a potential significant role in the development of radioresistance against repeated radiotherapy has prompted us to define the pathways by which OPN regulates lung cancer cell growth. In addition, autophagy has been reported to play a key role in the radiosensitization of cancer cells. Here, we report that increased OPN expression through induction of nuclear p53 following irradiation was inhibited by exogenous beclin-1 (BECN1). Our results clearly show that BECN1 gene expression led to induction of autophagy and inhibition of cancer cell growth and angiogenesis. Our results suggest that the induction of autophagy abrogated the radioresistance of the cancer cells. Interestingly, we showed that knockdown of OPN by lentivirus-mediated shRNA induced the autophagy of human lung cancer cell. Taken together, these results suggest that OPN and BECN1 can be molecular targets for overcoming radioresistance by controlling autophagy.
To explore the clip and the geometrical center displacements based on the four-dimensional computed tomography (4DCT) for external-beam partial breast irradiation (EB-PBI), fourteen breast cancer patients treated with breast-conserving surgery were recruited for EB-PBI and undertook 4DCT simulation during free breathing. The displacements of the selected clips and the geometrical center at left-right (LR), anterior-posterior (AP) and superior-inferior (SI) directions were measured. The comparison and the correlation of the displacement between the selected clips and the geometric center were analyzed. The displacements in AP and SI were greater than that in LR for the same selected clip (P < 0.05). Almost all the displacements of the geometrical center were greater than that of the selected clips in the same direction, (P < 0.05), except the displacements of lower clip in SI direction. The displacement of the geometric center showed a statistical correlation with the upper clip and lower clip in SI direction (both P < 0.05). Therefore, the internal margin in AP and SI directions should be greater than LR direction for the purpose of adequate target coverage and sparing more normal tissue. This study also indicates that the displacement of a single clip was not qualified to substitute for the displacement of the target based on all clips of the surgical cavity.
From 2007 to 2010, 230 patients had iodine-125 seeds implanted (loose or intra-operatively linked into seed trains with variable seed-to-seed spacing). The primary aim was to evaluate differences in implant quality by comparing the intra-operative and post-implant dosimetry in patients treated with loose and intra-operatively linked seeds. The secondary aim was to evaluate the "learning curve" for the procedure. The following parameters were compared: the radiation dose to 90% of the prostate volume (D90), the radiation dose to 30% of the urethral volume (DU30), the percentage of the prostate volume receiving 100% or 200% of the prescribed dose (V100 or V200, respectively), the percentage of the rectal volume receiving 100% of the prescribed dose (VR100), and the homogeneity index (HI). We obtained the following results for loose vs. intra-operatively linked seeds: D90 (Gy), 184.7 ± 15.0 vs. 177.9 ± 12.7 (p = 0.002); V100 (%), 95.5 ± 2.4 vs. 94.9 ± 3.2 (p = 0.206); V200 (%), 35.1 ± 7.5 vs. 24.3 ± 6,9 (p < 0.001); DU30 (Gy), 218.6 ± 24.1 vs. 197.4 ± 19.5 (p = 0.001); VR100 (cm3), 0.6 ± 0.47 vs. 0.3 ± 0.3 (p < 0.001); HI (%), 31.8 ± 7.3 vs. 44.0 ± 9.8 (p < 0.001). The advantages of intra-operatively linked seed implantation over loose seed implantation are a more homogeneous prostate dose and lower urethral and rectal doses. The disadvantage is a lower post-implant D90. Sufficient experience with the loose seed implantation procedure was obtained after the first 40 patients. There was essentially no learning curve when a new implantation method using intra-operatively linked seeds was subsequently initiated.
Purpose: We investigated the incidences of pericardial and pleural effusions after definitive radiotherapy with or without concurrent chemotherapy were analyzed retrospectively. Methods: One hundred and forty-seven patients with esophageal cancer received definitive radiotherapy or concurrent chemoradiotherapy (CCR). Follow-up chest Computed Tomography scans were reviewed to detect pericardial and pleural effusions. Adverse events were graded according to the Radiation Therapy Oncology Group Common Toxicity Criteria. Results: The median follow-up was 34 (range, 6 to 84) months. Numbers of eligible patients evaluated for pericardial and pleural effusions were 107 and 101, respectively. Pericardial effusions exceeding grade 1 and grade 2 toxicities were observed in 46 (43%) and 15 (14%) patients, respectively. The corresponding numbers for pleural effusions were 44 (44%) and 18 (18%). Onset of effusion ranged from 1 to 65 months after treatment. Multivariate analysis identified radiation field width of the mediastinum exceeding 8 cm as a significant risk factor for both pericardial and pleural effusions. Age and field length exceeding 20 cm were identified as independent risk factors for pleural effusion. Conclusions: Pericardial and pleural effusions after radiotherapy or CCR are occasionally recognized as adverse events in patients with esophageal cancer. The mediastinal radiation field width can be a simple indicator for predicting those adverse events.
CT perfusion imaging is a promising technique for delineating the target volume for three-dimensional conformal radiotherapy, but it is difficult in humans to obtain gross pathological samples at the same level of the brain tumor to evaluate this technique. The aim of this study was to use the BV map of CT perfusion imaging to assess the target volume in the rabbit VX2 brain tumor model, which has similar characteristics to human brain tumor, and compare the results to those of CECT. New Zealand white rabbits were used for the animal model. After tumor cell implantation 21 rabbits underwent 64-slice CT scanning. The target slice was selected and the maximum major axis length and minimum minor axis length of the tumor in the target slice on BV maps and contrast-enhanced CT images were measured. Pathological specimens were obtained from the rabbit brains which were removed intact. The GTV and CTV of the imaging methods were compared. Scanning was successful in 20 rabbits. The CECT images showed the target area for the VX2 tumor in 16 rabbits. The BV maps showed the target area for the tumor in 20 rabbits. The probability was 95% that the GTV determined by pathology can be covered completely when BV maps are used. CT perfusion imaging appears to be a promising technique for delineating the GTV of brain tumors in clinical practice.
This study aimed to investigate whether the combination of clinical information, tumor volume and pretreatment SUVmax at the primary tumors might improve the prognostic stratification in pharyngeal cancer (PC) patients treated with radiotherapy (RT). Sixty-two patients with PC (35 oropharynx; 27 hypopharynx) treated with RT were enrolled in this retrospective analysis. All patients received pretreatment FDG- PET or PET/CT. The primary tumor relapse-free survival (PRFS) was calculated according to different variables. The median values of the SUVmax for the primary tumors (SUVp-max) and the gross tumor volume (GTVp) were used to divide patients into two groups. Independent prognosticators were identified by the Cox regression analysis. In this study, the median SUVp-max and GTVp was 11 and 15.5 ml. Patients having tumors with SUVp-max > 11 had a significantly inferior 2-year PRFS (41% vs. 75%, p = 0.003) compared with patients having lower uptake tumors. Multivariate analysis of the PRFS showed two prognostic factors: SUVp-max > 11 (p = 0.04, hazard ratio = 2.67) and GTVp > 15.5 ml (p = 0.03, hazard ratio = 2.88). For patients with a GTVp less than 15.5 ml, there was a more significant impact of SUVmax-p on their PRFS compared to that for those with large ones. We disclosed a higher pretreatment SUVp-max is a predictor for primary recurrence in PC patients treated with RT, particularly for those with smaller tumor volumes. Patients with a large tumor volume or a higher SUVp-max should be considered for requiring more aggressive treatment approaches.
To improve treatment conformity for prostate cancer, we investigated daily applicator displacement during high-dose-rate interstitial brachytherapy (HDR-ISBT). Thirty patients treated with HDR-ISBT as monotherapy were examined. All patients received a treatment dosage of 49 Gy per 7 fractions over 4 days. For dose administration, we examined 376 flexible applicators (1128 points) using our unique ambulatory implant technique. Using CT images with a 3-mm slice thickness, we calculated the relative coordinates of the titanium markers and the tips of the applicators. We calculated the distance between the center of gravity of the markers and the tips of the catheters, and compared the distances measured on the day of implantation and the second, third, and fourth treatment days. The mean displacement distance for all applicators was 4.3 ± 3.4 mm, 4.6 ± 4.1 mm, and 5.8 ± 4.5 mm at 21, 45, and 69 hours after initial planning CT. We used a 15-mm margin for needle displacement and only 2 points of 2 patients (16 mm and 18 mm at 69 hours, 2/1128 = 0.2%) exceeded this range. Almost patients (87%) showed the largest displacement within the first 21 hours. The relative doses that covered 100% of CTV (D100(CTV)) values compared with the initial treatment plan were reduced to 0.96 ± 0.08, 0.96 ± 0.08 and 0.94 ± 0.1 at 21, 45 and 69 hours. However, the relative D90(CTV) values kept acceptable levels (1.01 ± 0.02, 1.01 ± 0.03 and 1.01 ± 0.03). Cranial margin of 15 mm seems to be effective to keep D90(CTV) level if we do not do corrective action.
The microbeam irradiation system (Single-Particle Irradiation System to Cell, acronym as SPICE) at the National Institute of Radiological Sciences (NIRS), Japan, was employed to irradiate dechorionated zebrafish embryos at the 2-cell stage at 0.75 h post fertilization (hpf) by microbeam protons. Either one or both of the cells of the embryos were irradiated with 10, 20, 40, 50, 80, 100, 160, 200, 300 and 2000 protons each with an energy of 3.37 MeV. The embryos were then returned back to the incubator until 24 hpf for analyses. The levels of apoptosis in zebrafish embryos at 25 hpf were quantified through terminal dUTP transferase-mediated nick end-labeling (TUNEL) assay, with the apoptotic signals captured by a confocal microscope. The results revealed a triphasic dose-response for zebrafish embryos with both cells irradiated at the 2-cell stage, namely, (1) increase in apoptotic signals for < 200 protons (< 30 mGy), (2) hormesis to reduce the apoptotic signals below the spontaneous number for 200–400 protons (at doses of 30–60 mGy), and (3) increase in apoptotic signals again for > 600 protons (at doses > 90 mGy). The dose response for zebrafish embryos with only one cell irradiated at the 2-cell stage was also likely a triphasic one, but the apoptotic signals in the first zone (< 200 protons or < 30 mGy) did not have significant differences from those of the background. At the same time, the experimental data were in line with induction of radiation-induced bystander effect as well as rescue effect in the zebrafish embryos, particular in those embryos with unirradiated cells.
The radiation induced bystander response is defined as a response in cells which have not been directly targeted by radiation, but which are in the neighborhood of cells which have been directly exposed. In many cases, the bystander response is saturated with increasing dose and is observed when only one cell in a population is targeted by high-LET particle radiations or ultrasoft X-rays (278 eV). However, in our studies using synchrotron X-ray microbeams (5.35 keV), the bystander cell killing effect in normal human fibroblast WI-38 cells had a parabolic relationship to the irradiating dose and was detected if 5 or more cell nuclei were irradiated. To evaluate the feature of the X-ray-induced bystander cell killing effect at a wider dose range and the existence of photon energy dependence, the effects were assessed by irradiating cell nuclei in confluent WI-38 cells with AlK X-ray microbeams (1.49 keV). The surviving fraction decreased when only a single cell nucleus was irradiated, suggesting the minimal number of targeted cells to induce the effect may depend on the energy of photons used. In this study, we found that the bystander cell killing effect showed a biphasic relationship to the irradiating dose. The decrease in bystander cell survival at the doses higher than 0.23 Gy was partially suppressed between 2.3 and 7.0 Gy, followed by level-off around 90% above 14 Gy, suggesting that the X-ray-induced bystander response is dose dependent. In addition, NO is one of chief initiators/mediators of the effect at least 0.47 Gy.
This is a pilot study that aims to elucidate regional disparities in the distribution of medical resources in Japan. For this purpose, we employed the Gini coefficient (GC) in order to analyze the distribution of radiotherapy resources, which are allocated to each prefecture in Japan depending on the size of its population or physical area. Our study used data obtained from the 2005 and 2007 national surveys on the structure of radiation oncology in Japan, conducted by the Japanese Society for Therapeutic Radiology and Oncology (JASTRO). Our analysis showed that the regional disparities regarding the radiation oncologists and radiotherapy technologists were small, and concluded that such resources were almost equitably distributed. However, medical physicists are inequitably distributed. Thus, policymakers should create and implement measures to train and retain medical physicists in areas with limited radiotherapy resources. Further, almost 26% of the secondary medical service areas lacked radiotherapy institutions. We attribute this observation to the existence of tertiary medical service areas, and almost all of prefectures face a shortage of such resources. Therefore, patients' accessibility to these resources in such areas should be improved.
We retrospectively evaluated the relationship between computed tomography (CT)- and histopathological findings of parotid and submandibular glands in six patients treated for advanced oral cancer. Eligibility criteria were a pathologic diagnosis of oral squamous cell carcinoma, preoperative chemoradiation therapy (CRT) with a total dose of 30 Gy and oral S-1 (80 mg/m2/day), the availability of morphological assessments by CT and of functional assessments with the Saxon test before- and 2 weeks after CRT, and the availability of histopathological slides of irradiated parotid and submandibular glands. In the histopathological interpretation, gland structures were divided into acinar-, duct-, and adipose cells and other tissues. The Mann-Whitney test and the Spearman rank correlation test were used to determine histopathological changes. After 30-Gy irradiation, saliva production and parotid and submandibular volumes were significantly decreased (P < 0.05 each). Histopathological analysis demonstrated that 30-Gy irradiation resulted in a loss of acinar cells although acinar cells in the submandibular gland were relatively retained; the median acinar rate in the parotid and submandibular glands was 1.1% and 19.0%, respectively. The CT values after CRT were inversely correlated with adipose ratios (r = –0.98, P < 0.01) and there was a strong correlation between CT values before and after CRT (r = 0.97, P < 0.01). Our results suggested that acinar cell loss is a main contributor to changes in the volume and function of irradiated human parotid and submandibular glands. The CT value may reflect the adipose ratio rather than salivary function.
An association between DNA repair gene polymorphisms, environmental factors, and development of some types of cancer has been suggested by several studies. Chronic lymphocytic leukemia (CLL) is the most common form of leukemia in the clean-up workers of the Chernobyl Nuclear Power Plant (NPP) accident and it has some specific features. Therefore, we have studied the possible differences in DNA repair gene polymorphisms in CLL patients depending on ionizing radiation (IR) exposure history and their clinical characterictics. Arg399Gln XRCC1, Thr241Met XRCC3, and Lys751Gln XPD polymorphisms were studied in 64 CLL patients, exposed to IR due to the Chernobyl NPP accident, 114 IR-non-exposed CLL patients, and 103 sex- and age-matched IR-exposed controls using polymerase chain reaction-restriction fragment-length polymorphism analysis. All investigated polymorphisms were equally distributed between two groups of CLL patients and IR-exposed controls, except that that there was a significant reduction of the common homozygous Lys/Lys XPD genotype among IR-exposed CLL patients (23.7%) compared with IR-exposed controls (45.6%), OR = 0.37; 95% CI = 0.18–0.75; (P = 0.005). The number of IR-non-exposed CLL patients (37.4%) with the Lys/Lys XPD genotype was also decreased compared to IR-exposed controls, although this difference was not significant (P = 0.223). These preliminary data suggest a possible modifying role of Lys751Gln XPD polymorphism for the development of CLL, expecially in radiation-exposed persons.