Radiation effects on human heredity.

In experimental organisms such as fruit flies and mice, increased frequencies in germ cell mutations have been detected following exposure to ionizing radiation. In contrast, there has been no clear evidence for radiation-induced germ cell mutations in humans that lead to birth defects, chromosome aberrations, Mendelian disorders, etc. This situation exists partly because no sensitive and practical genetic marker is available for human studies and also because the number of people exposed to large doses of radiation and subsequently having offspring was small until childhood cancer survivors became an important study population. In addition, the genome of apparently normal individuals seems to contain large numbers of alterations, including dozens to hundreds of nonfunctional alleles. With the number of mutational events in protein-coding genes estimated as less than one per genome after 1 gray (Gy) exposure, it is unsurprising that genetic effects from radiation have not yet been detected conclusively in humans.

Associations of clinical and dosimetric parameters with late rectal toxicities after radical intensity-modulated radiation therapy for prostate cancer: a single-centre retrospective study.

INTRODUCTION: This study assessed the incidence of late rectal toxicities and evaluated potential predictive factors for late proctitis in patients treated with prostate-specific intensity-modulated radiotherapy in Hong Kong. METHODS: This retrospective longitudinal observational study included patients with localised prostate cancer who were treated with intensity-modulated radiation therapy in an oncology unit in Hong Kong between January 2007 and December 2011, and who had >1 year of follow-up. Clinical, pharmacological, and radiation parameters were recorded. Toxicities were measured by Common Terminology Criteria for Adverse Events version 4. RESULTS: In total, 232 patients were included in this analysis. The mean follow-up time was 7.3 ± 2.1 years and 46.5% of the patients had late rectal toxicities. Late proctitis occurred in 30.5% of patients; 25% of the patients with late proctitis exhibited grade ≥2 toxicity. Median onset times for late proctitis and rectal bleeding were 15 and 18.4 months, respectively. Multivariable regression showed increased odds for the occurrence of late proctitis in patients with older age (odds ratio [OR]=1.11, 95% confidence interval [CI]=1.04-1.19, P=0.003), higher V70 (OR=1.08, 95% CI=1.01-1.15, P=0.027), and presence of acute rectal toxicities (OR=4.47, 95% CI=2.37-8.43, P<0.001). Antiplatelet use was not significantly associated with the occurrence of late proctitis (OR=1.98, 95% CI=0.95-4.14, P=0.07). CONCLUSIONS: The incidence of late rectal toxicities was considerable among patients in this study. Clinicians should consider the possibility of late proctitis for patients with older age, acute rectal toxicities, and higher V70. High doses to rectal volumes should be limited because of the significant association with V70.

Autologous fat graft in irradiated orbit postenucleation for retinoblastoma.

Autologous fat grafting has been extensively and successfully adopted in a number of pathologic conditions in regenerative surgery especially on irradiated fields in order to improve pain symptoms and tissue trophism promoting scar release. In the present study, we report our experience with autologous fat grafting for the treatment of postirradiation fibrosis and pain on three consecutive patients undergoing orbital enucleation for locally advanced retinoblastoma (RB) and subsequent radiotherapy. We selected three consecutive patients who underwent orbital enucleation for locally advanced RB and subsequent local radiotherapy showing severe reduction in orbital volume and eyelid length and retraction due to fibrosis, spontaneous local pain exacerbated after digital pressure with no possibility to place an ocular implant. They underwent autologous fat grafting in the orbital cavity and results were evaluated by clinical examination at 5 and 14 days, and 1, 3, 6 months, and 1 year after surgery. A significant release of scar retraction, reduction of fibrosis and orbital rim contraction together with an important improvement of pain symptoms was observed in all patients. The local changes observed enabled an ease placement of an ocular prosthetic implant (implant). No local or systemic complication occurred. Fat grafting is a promising treatment for patients showing radiotherapy related complication in the orbital area and it should be adopted by all oculoplastic surgeon in order to improve pain syndrome creating the ideal local conditions for the placement of an ocular prosthetic implant.

Social behavioral testing and brain magnetic resonance imaging in chicks exposed to mobile phone radiation during development.

BACKGROUND: The potential adverse effect of mobile phone radiation is currently an area of great concern in the field of public health. In the present study, we aimed to investigate the effect of mobile phone radiation (900 MHz radiofrequency) during hatching on postnatal social behaviors in chicks, as well as the effect on brain size and structural maturity estimated using 3.0 T magnetic resonance imaging. At day 4 of incubation, 76 normally developing chick embryos were divided into the control group (n = 39) and the radiation group (n = 37). Eggs in the radiation group were exposed to mobile phone radiation for 10 h each day from day 4 to 19 of incubation. Behavioral tests were performed 4 days after hatching. T2-weighted MR imaging and diffusion tensor imaging (DTI) were subsequently performed. The size of different brain subdivisions (telencephalon, optic lobe, brain stem, and cerebellum) and corresponding DTI parameters were measured. The Chi-square test and the student's t test were used for statistical analysis. P < 0.05 was considered statistically significant. RESULTS: Compared with controls, chicks in the radiation group showed significantly slower aggregation responses (14.87 ± 10.06 vs. 7.48 ± 4.31 s, respectively; P < 0.05), lower belongingness (23.71 ± 8.72 vs. 11.45 ± 6.53 s, respectively; P < 0.05), and weaker vocalization (53.23 ± 8.60 vs. 60.01 ± 10.45 dB/30 s, respectively; P < 0.05). No significant differences were found between the radiation and control group for brain size and structural maturity, except for cerebellum size, which was significantly smaller in the radiation group (28.40 ± 1.95 vs. 29.95 ± 1.41 cm(2), P < 0.05). The hatching and heteroplasia rates were also calculated and no significant difference was found between the two groups. CONCLUSIONS: Mobile phone radiation exposure during chick embryogenesis impaired social behaviors after hatching and possibly induced cerebellar retardation. This indicates potential adverse effects of mobile phone radiation on brain development.

Maternal occupational exposure to ionizing radiation and major structural birth defects.

BACKGROUND: Ionizing radiation (IR) is known to be carcinogenic and mutagenic, but little is known about the association between maternal occupational exposure to IR and birth defects. METHODS: We studied 38,009 mothers who participated in the National Birth Defects Prevention Study and delivered between 1997 and 2009. We assessed odds ratios [ORs] for the association between maternal occupations with potential exposure to IR and 39 birth defects. RESULTS: We observed significant odds ratios (ORs) for isolated hydrocephaly (adjusted OR [AOR], 2.1; 95% confidence interval [CI], 1.1-4.2), isolated anotia/microtia (AOR, 2.0; 95% CI, 1.0-4.0), isolated colonic atresia (crude OR, 7.5; 95% CI, 2.5-22.3), isolated omphalocele (AOR, 2.3; 95% CI, 1.1-4.6) and isolated anencephaly (crude OR, 0.23; 95% CI, 0.06-0.94). We also observed a nonsignificant OR for birth defects in aggregate (AOR, 2.0; 95% CI, 0.9-4.6) among mothers with potential occupational exposure to fluoroscopy. CONCLUSION: We assessed 39 birth defects, observing that maternal occupations with potential exposure to IR were associated with a significantly increased risk for 4 birth defects and a significantly protected risk for 1 birth defect. These results should be interpreted cautiously because our measurement of exposure is qualitative, some of these associations may be due to occupational exposures that are correlated with IR and some may be due to chance. However, these findings serve as the first evaluation of these relationships in a large study and may be useful for generating hypotheses for future studies.

The fisherman's cards: how to address past and future radiation exposures in clinical decision making.

OBJECTIVE. The purpose of this article is to describe how to address patients' past-and future potential-radiation exposures when making an imaging decision in a given situation. CONCLUSION. The Biologic Effects of Ionizing Radiation committee has endorsed a linear no-threshold model to explain the relationship between radiation exposure and cancer risk. This model implies that past and future potential exposures should not impact current decisions. We present an analogy that deconstructs these counterintuitive conclusions and facilitates translation of key radiation risk principles to practice.

Pregnancy after successful cancer treatment: what needs to be considered?

Over the last decade, advances in oncology led to improved treatment results and increasing numbers of long-term cancer survivors. Fulfilling the desire to have children is important for many patients after cancer treatment. Consequently, oncologists, gynecologists and obstetricians are seeing more patients who wish to conceive after treatment. The necessary prerequisites that should be considered when supporting a planned pregnancy after cancer treatment are discussed in this article. The possible consequences of chemotherapy and radiotherapy on the course of pregnancy and the health of the offspring, as well as the interactions between cancer and pregnancy, are reviewed with the focus on childhood cancer, malignant lymphomas, and breast cancer. Despite chemo- or radiotherapy, neither the teratogenic risk nor the risk of adventitious cancers appears to be increased for the offspring of cancer survivors. However, there is a slightly higher risk of miscarriage after chemotherapy. In case of radiation to the uterus, there is a higher risk of premature birth, intrauterine growth retardation, and increased perinatal mortality. The effect is more pronounced after prepubertal radiation than for postpubertal radiation. The former cancer patient's desire to conceive can nevertheless be supported, given that pregnancy and birth are closely monitored.

Adaptive response of low linear energy transfer X-rays for protection against high linear energy transfer accelerated heavy ion-induced teratogenesis.

BACKGROUND: Adaptive response (AR) of low linear energy transfer (LET) irradiations for protection against teratogenesis induced by high LET irradiations is not well documented. In this study, induction of AR by X-rays against teratogenesis induced by accelerated heavy ions was examined in fetal mice. METHODS: Irradiations of pregnant C57BL/6J mice were performed by delivering a priming low dose from X-rays at 0.05 or 0.30 Gy on gestation day 11 followed one day later by a challenge high dose from either X-rays or accelerated heavy ions. Monoenergetic beams of carbon, neon, silicon, and iron with the LET values of about 15, 30, 55, and 200 keV/µm, respectively, were examined. Significant suppression of teratogenic effects (fetal death, malformation of live fetuses, or low body weight) was used as the endpoint for judgment of a successful AR induction. RESULTS: Existence of AR induced by low-LET X-rays against teratogenic effect induced by high-LET accelerated heavy ions was demonstrated. The priming low dose of X-rays significantly reduced the occurrence of prenatal fetal death, malformation, and/or low body weight induced by the challenge high dose from either X-rays or accelerated heavy ions of carbon, neon or silicon but not iron particles. CONCLUSIONS: Successful AR induction appears to be a radiation quality event, depending on the LET value and/or the particle species of the challenge irradiations. These findings would provide a new insight into the study on radiation-induced AR in utero.

Developmental defects and genomic instability after x-irradiation of wild-type and genetically modified mouse pre-implantation and early post-implantation embryos.

Results obtained from the end of the 1950s suggested that ionizing radiation could induce foetal malformations in some mouse strains when administered during early pre-implantation stages. Starting in 1989, data obtained in Germany also showed that radiation exposure during that period could lead to a genomic instability in the surviving foetuses. Furthermore, the same group reported that both malformations and genomic instability could be transmitted to the next generation foetuses after exposure of zygotes to relatively high doses of radiation. As such results were of concern for radiation protection, we investigated this in more detail during recent years, using mice with varying genetic backgrounds including mice heterozygous for mutations involved in important cellular processes like DNA repair, cell cycle regulation or apoptosis. The main parameters which were investigated included morphological development, genomic instability and gene expression in the irradiated embryos or their own progeny. The aim of this review is to critically reassess the results obtained in that field in the different laboratories and to try to draw general conclusions on the risks of developmental defects and genomic instability from an exposure of early embryos to moderate doses of ionizing radiation. Altogether and in the range of doses normally used in diagnostic radiology, the risk of induction of embryonic death and of congenital malformation following the irradiation of a newly fertilised egg is certainly very low when compared to the 'spontaneous' risks for such effects. Similarly, the risk of radiation induction of a genomic instability under such circumstances seems to be very small. However, this is not a reason to not apply some precaution principles when possible. One way of doing this is to restrict the use of higher dose examinations on all potentially pregnant women to the first ten days of their menstrual cycle when conception is very unlikely to have occurred (the so-called ten-day rule), as already recommended by the Health Protection Agency. Such a precautionary attitude would also be supported by the uncertainties associated with later changes in gene expression which might result from irradiation or early embryos with moderate doses.

SCAI consensus document on occupational radiation exposure to the pregnant cardiologist and technical personnel.

Concerns regarding radiation exposure and its effects during pregnancy are often quoted as an important barrier preventing many women from pursuing a career in Interventional Cardiology. Finding the true risk of radiation exposure from performing cardiac catheterization procedures can be challenging and guidelines for pregnancy exposure have been inadequate. The Women in Innovations group of Cardiologists with endorsement of the Society for Cardiovascular Angiography and Interventions aim to provide guidance in this publication by describing the risk of radiation exposure to pregnant physicians and cardiac catheterization personnel, to educate on appropriate radiation monitoring and to encourage mechanisms to reduce radiation exposure. Current data do not suggest a significant increased risk to the fetus of pregnant women in the cardiac catheterization laboratory and thus do not justify precluding pregnant physicians from performing procedures in the cardiac catheterization laboratory. However, radiation exposure among pregnant physicians should be properly monitored and adequate radiation safety measures are still warranted.

[Principal inferences from studies of radiobiological effects for radiation protection purposes].

The most recent Recommendations (Publication 103) issued by the International Commission for Radiological Protection (ICRP) are based on the data that have been published since 1990 up to now. The basic task of the ICRP Committee 1 was to formulate the key implications of studies on radiobiological effects for the purposes of radiological protection. Presented in the paper are the new achievements in the field of biology, radiobiology and radiation epidemiology which were taken into account by the ICRP in the process of Publication 103 preparation. The Recommendations provide present-day values of weighting factors for radiation exposure and tissue weighting factors, as well as radiation detriment and radiogenic risk factors for cancer and genetic diseases. Also considered are tissue reactions to radiation exposure, consequences of in utero exposure and the risks of developing non-cancer diseases for exposed individuals. It should be noted that the key inferences and recommendations are to a considerable degree related to biological effects accounted for by acute and chronic exposure to ionizing radiation in the range of small doses (up to 100 mSv).

Dose Fractionation During Puberty Is More Detrimental to Mammary Gland Development Than an Equivalent Acute Dose of Radiation Exposure.

PURPOSE: Computed tomographic (CT) scans in adolescents have increased dramatically in recent years. However, the effects of cumulative low-dose exposures on the development of radiation sensitive organs, such as the mammary gland, is unknown. The purpose of this work was to define the effects of dose rate on mammary organ formation during puberty, an especially sensitive window in mammary development. We used a fractionated low-dose x-ray exposure to mimic multiple higher dose CT scans, and we hypothesized that fractionated exposure would have less of an effect on the number of mammary gland defects compared with an acute exposure. METHODS AND MATERIALS: Female mice were subjected to fractionated low-dose x-ray exposure (10 cGy/d for 5 days), acute x-ray exposure (1 × 50 cGy), or sham exposure. As the wide genetic diversity in humans can play a role in a person's response to irradiation, 2 genetically diverse mouse strains differing in radiation sensitivity (BALB/c-sensitive; C57BL/6-resistant) were used to investigate the role of genetic background on the magnitude of the effect. RESULTS: Unexpectedly, our data reveal that multiple low-dose exposures produce greater immune and mammary defects for weeks after exposure compared with controls. The most pronounced defects being increased ductal branching in both strains and a greater percentage of terminal end buds in the BALB/c strain of mice exposed to fractionated radiation compared with sham. Radiation-induced defects near the terminal end bud were also increased in both strains. CONCLUSIONS: The findings suggest that fractionated low-dose exposures are potentially more damaging to organ development compared with an equivalent, single acute exposure and that genetic background is an important parameter modifying the severity of these effects.

Chronic radiation exposure in the Rivne-Polissia region of Ukraine: implications for birth defects.

OBJECTIVES: The health effects of chronic low-dose radiation exposure remains a controversial question. Monitoring after the Chernobyl nuclear accident in Ukraine suggested that chronic low-dose radiation exposure was not linked to cancer mortality among the general population. However, elevated rates of birth defects in contaminated compared to uncontaminated regions suggest that exposure to radiation in utero might impact development and that chronic radiation exposure might represent an underestimated risk to human health. METHODS: We sought to determine current radiation exposure routes in Rivne-Polissia, a region of Ukraine contaminated by the Chernobyl accident. This represents a first step toward comprehensive studies of the effects of chronic radiation exposure on human health. We designed and administered a dietary and activity survey to 344 women in Polissia. We assessed types and sources of food consumed, types of outdoor activities, and alcohol intake. RESULTS: Alcohol intake was low and alone does not account for the observed high rates of birth defects. Wild foods, especially mushrooms and berries, and locally produced foods, especially milk related, were major radiation exposure routes. Additionally, women were exposed to radiation through inhalation while burning grasses and potato vines in fields, and wood for cooking and heating. CONCLUSIONS: Twenty four years after the Chernobyl accident, women continue to be chronically exposed to low-dose radiation at levels exceeding current recommendations. This might contribute (especially synergistically with alcohol consumption and micronutrient deficiencies) to higher prevalence of birth defects in areas of Ukraine with high levels of radiation contamination compared to uncontaminated areas.

[Dynamics of gonadal dysgenesis frequency in Drosophila melanogaster under controlled conditions of chronic radiation exposure].

Two Drosophila melanogaster strains (Canton-S and ri-lines) for 20 generations were in the controlled terms of chronic irradiation with 3-dose rate (1,2 x 10(-8); 0,3 x 10(-8); 0,12 x 10(-8) Gy/c). The dynamics of hybrid dysgenesis frequency was explored for each generation of F1 descendants from Canton-S and ri-lines crossing. The gradual change of dose response of hybrid dispense depending on duration of irradiation of ancestors and dose rate was shown. The complex dynamics of hybrid dysgenesis frequency depending on irradiation duration of ancestors and dose rate was detected. The cumulative effect of the prolonged irradiation shows up as adaptation at the lowest dose rate and as exhaustion at the highest dose rate. Question comes into discussion about the features of transitional process and including of protective and adaptive reactions hierarchy at the conditions of radiation factor chronic action.

[Bioelectrical activity of the myocardium in children born to parents irradiated during the Chernobyl disaster with isolated abnormal chords of the left ventricle].

A total 156 children of the main group (children born to parents irradiated during the Chernobyl disaster), who according to echocardiography revealed a different number of isolated abnormal chords of the left ventricle, 20 healthy children, 24 children of nosological control group and 50 children of referent group have been observed. It was found that isolated AHLV in children born to irradiated parents, was associated with changes in standard ECG, reflecting the presence of arrhythmias or predictors of their development. No significant differences in subgroups of children with different number of isolated AHLV have been established. Children with isolated AHLV born to parents irradiated during the Chernobyl accident, as all patients with minor structural anomalies of the heart, should be refered to a risk group in connection with the possibility of the development, in the first place, ventricular extrasystoles, paroxysmal ventricular tachycardia. Early diagnosis of isolated AHLV will allow to assess the outlook for further course of the disease and develop a plan of treatment and preventive measures.

[Autonomic homeostasis of children born to parents irradiated in the result of the Chernobyl catastrophe with isolated abnormal chords of the left ventricle].

156 children of the main group (were born to parents irradiated in the result of Chernobyl disaster), in which according to Doppler echocardiography isolated abnormal chords of the left ventricle (AHLV) identified, 44 children of control group and 50 children of referent group were involved in the study Analysis of indicators of operational regulation of heart rate in children of primary group indicate the existence of autonomic dysregulation, which has the maximum expression in children with a threshold number of isolated abnormal chords. Evidence of autonomic dysregulation in children born to parents irradiated in the result of the Chernobyl disaster with isolated AHLV requires primary and secondary prevention to reduce the frequency of unfavourable clinical course.

Ionizing radiation-induced gene modulations, cytokine content changes and telomere shortening in mouse fetuses exhibiting forelimb defects.

Several lines of evidence have linked limb teratogenesis to radiation-induced apoptosis and to the p53 status in murine fetuses. In previous reports, we studied the occurrence of various malformations after intrauterine irradiation and showed that these malformations were modulated by p53-deficiency as well as by the developmental stage at which embryos were irradiated. In this new study, we focused onto one particular phenotype namely forelimb defects to further unravel the cellular and molecular mechanisms underlying this malformation. We measured various parameters expected to be directly or indirectly influenced by irradiation damage. The mouse fetuses were irradiated at day 12 p.c. (post conception) and examined for forelimb defects on gestational days 15, 16, 17 and 19 of development. The release of inflammatory cytokines was determined in the amniotic fluid on day 16 p.c. and the mean telomere lengths assessed at days 12, 13 and 19 p.c. Differential gene expression within the forelimb bud tissues was determined using Real Time quantitative PCR (RTqPCR) 24 h following irradiation. Apoptosis was investigated in the normal and malformed fetuses using the TUNEL assay and RTqPCR. First, we found that irradiated fetuses with forelimb defects displayed excessive apoptosis in the predigital regions. Besides, overexpression of the pro-apoptotic Bax gene indicates a mitochondrial-mediated cell death. Secondly, our results showed overexpression of MKK3 and MKK7 (members of the stress-activated MAP kinase family) within the malformed fetuses. The latter could be involved in radiation-induced apoptosis through activation of the p38 and JNK pathways. Thirdly, we found that irradiated fetuses exhibiting forelimb defects showed a marked telomere shortening. Interestingly, telomere shortening was observed as the malformations became apparent. Fourthly, we measured cytokine levels in the amniotic fluid and detected a considerable inflammatory reaction among the irradiated fetuses as evidenced by the increase in pro-inflammatory cytokine levels. Altogether, our data suggest that transcriptional modulations of apoptotic, inflammation, stress, and DNA damage players are early events in radiation-induced forelimb defects. These changes resulted in harsh developmental conditions as indicated by a marked increase in cytokine levels in the amniotic fluid and telomere shortening, two features concomitant with the onset of the forelimb defect phenotype in our study.

Teratological evaluation of mouse fetuses exposed to a 20 kHz EMF.

As a continuation of our previous study, we performed a teratological evaluation of the importance of gestational age with regards to the exposure of 20 kHz intermediate frequency magnetic field (IF) on pregnant ICR mice. The pregnant mice were exposed to a 20 kHz IF magnetic field for 8 h/day in a carousel irradiator at 30 microT which is the limit standard for occupational population in Korea. The animals were sacrificed on the 18th day of gestation and the fetuses were examined for mortality, growth retardation, changes in head size and other morphological abnormalities. We concluded that exposure to 30 microT with 20 kHz IF did not cause any observable adverse effects on mouse fetuses.