Richard G. E. Haylock

Risks of brain tumour following treatment for cancer in childhood: modification by genetic factors, radiotherapy and chemotherapy.

A cohort of 4,400 persons treated for various cancers of childhood in France and the UK was followed up over an extended period to assess risks of subsequent brain tumour in relation to the radiotherapy and chemotherapy that the children received for their first cancer. Elevated risks of subsequent brain tumours were associated with first central nervous system (CNS) tumour (two‐sided p =0.0002) and neurofibromatosis (two‐sided p =0.001). There was also elevated brain tumour risk (two‐sided p =0.003) associated with ionising radiation exposure, the risk being concentrated among benign and unspecified brain tumours. The radiation‐related risk of benign and unspecified brain tumours was significantly higher than that of malignant brain tumours (two‐sided p≤ 0.05); there was no significant change of malignant brain tumour risk with ionising radiation dose (two‐sided p > 0.2). In general, there were no strong associations between alkylating agent dose and brain tumour risk. The only significant association between brain tumour risk and alkylating agent dose was in relation to compounds used (bleomycin, chloraminophen) that are thought not to deliver substantial doses to the brain; the statistical significance of the trend with dose depended on a single case, and thus must be considered a weak result. Int. J. Cancer 78:269–275, 1998. Published 1998 Wiley‐Liss, Inc.

Low‐level exposure to pulsed 900 MHz microwave radiation does not cause deficits in the performance of a spatial learning task in mice

There is some concern that short-term memory loss or other cognitive effects may be associated with the use of mobile cellular telephones. In this experiment, the effect of repeated, acute exposure to a low intensity 900 MHz radiofrequency (RF) field pulsed at 217 Hz was explored using an appetitively-motivated spatial learning and working memory task. Adult male C57BL/6J mice were exposed under far field conditions in a GTEM cell for 45 min each day for 10 days at an average whole-body specific energy absorption rate (SAR) of 0.05 W/kg. Their performance in an 8-arm radial maze was compared to that of sham-exposed control animals. All behavioral assessments were performed without handlers having knowledge of the exposure status of the animals. Animals were tested in the maze immediately following exposure or after a delay of 15 or 30 min. No significant field-dependent effects on performance were observed in choice accuracy or in total times to complete the task across the experiment. These results suggest that exposure to RF radiation simulating a digital wireless telephone (GSM) signal under the conditions of this experiment does not affect the acquisition of the learned response. Further studies are planned to explore the effects of other SARs on learned behavior. Bioelectromagnetics 21:151-158, 2000. Published 2000 Wiley-Liss, Inc.

Deficits in spatial learning after exposure of mice to a 50 Hz magnetic field

A series of four experiments was performed to determine the effect of exposure to a 50 Hz magnetic field on memory-related behaviour of adult, male C57BL/6J mice. Experimental subjects were exposed to a vertical, sinusoidal magnetic field at 0.75 mT (rms), for 45 min immediately before daily testing sessions on a spatial learning task in an eight-arm radial maze. Control subjects were only exposed to a background time-varying field of less than 50 nT and the ambient static field of about 40 microT. In each experiment, exposure significantly reduced the rate of acquisition of the task but did not affect overall accuracy. This finding is consistent with the results of another study that found that prior exposure to 60 Hz magnetic fields affected spatial learning in rats.

Prenatal Irradiation and Spatial Memory in Mice: Investigation of Dose-response Relationship

Pregnant CD1 mice were exposed on gestational day 18 to 250 kV X-rays at 0.1, 0.25, 0.35 and 0.5 Gy. The performances of 10 adult male offspring from each exposure condition were investigated on a spatial discrimination learning task in a radial arm maze. An impairment in the performance of this task was found which showed a correlation with dose. Compared with sham exposed control mice, performance was not significantly affected with irradiation at 0.1 Gy and was slightly but non-significantly reduced at 0.25 Gy. Irradiation at 0.35 Gy caused a significant impairment in performance, and exposure at 0.5 Gy resulted in a still larger impairment. The overall association between dose and behavioural impairment was best described by a linear relationship without a threshold, although at doses lower than about 0.25 Gy any impairment would appear to be too small to be detectable.

50 Hz magnetic field effects on the performance of a spatial learning task by mice

Intense magnetic fields have been shown to affect memory-related behaviours of rodents. A series of experiments was performed to investigate further the effects of a 50 Hz magnetic field on the foraging behaviour of adult, male C57BL/6J mice performing a spatial learning task in an eight-arm radial maze. Exposure to vertical, sinusoidal magnetic fields between 7.5 microT and 7.5 mT for 45 min immediately before daily testing sessions caused transient decreases in performance that depended on the applied flux density. Exposure above a threshold of between 7.5 and 75 microT significantly increased the number of errors the animals made and reduced the rate of acquisition of the task without any effect on overall accuracy. However, the imposition of a 45-minute delay between exposure at 0.75 mT and behavioural testing resulted in the elimination of any deficit. Similarly, exposure to fields between 7.5 microT and 0.75 mT for 45 min each day for 4 days after training had no amnesic effects on the retention and subsequent performance of the task. Overall, these results provide additional evidence that 50 Hz magnetic fields may cause subtle changes in the processing of spatial information in mice. Although these effects appear dependent on field strength, even at high flux densities the field-induced deficits tend to be transient and reversible.

Modelling lung tumour risk in radon-exposed uranium miners using generalizations of the two-mutation model of Moolgavkar, Venzon and Knudson.

Purposes : To model radon-induced lung cancer in uranium miners using a quasi-biological model of carcinogenesis. Materials and methods : Fitting of generalizations of the stochastic two-mutation carcinogenesis model of Moolgavkar, Venzon and Knudson to a case-control dataset nested within the cohort and to the full cohort of lung cancer mortality in the Colorado Plateau uranium miners, taking account of exposure to cigarette smoke and to radon daughters. Results : Models with three mutations gave adequate descriptions of the time and age patterns of radon-daughter-induced excess lung tumour mortality. The overall fit of the two-mutation model to the case-control data was somewhat worse than that of the three-mutation model. For both the optimal two- and threemutation models radon daughters and cigarette smoke were assumed to act on the first mutation rate. In the optimal twomutation model, radon daughters also modified the intermediate cell death or differentiation rate. In the optimal three-mutation model, radon daughters modified the second mutation rate. In all models, the action of radon daughters and cigarette smoke was markedly non-linear, particularly in their action on the mutation rates. The optimal two- and three-mutation models fitted to the cohort data were of slightly different form to those fitted to the case-control data. The model fits to the cohort data are preferred to those to the case-control data on grounds of plausibility. Conclusions : Quasi-biological carcinogenesis models with three mutations give adequate descriptions of the time and age patterns of radon-daughter-induced excess lung tumour mortality. The overall fit of the two-mutation model is somewhat worse than that of the three-mutation model.

Follow up of mortality and incidence of cancer 1952–98 in men from the UK who participated in the UK's atmospheric nuclear weapon tests and experimental programmes

Aims: To extend and analyse follow up of mortality and cancer incidence among men who took part in the UKs atmospheric nuclear weapon tests and experimental programmes 40–50 years ago, with particular reference to multiple myeloma and leukaemia. Methods: A total of 21 357 servicemen and male civilians from the UK who participated in the tests and a control group of 22 333 male controls were followed over the period 1952–98. Analyses were conducted of mortality from various causes, and of mortality and incidence for 27 types of cancer. Results: Rates of mortality from all causes continued to be similar among test participants and controls with the longer follow up, with standardised mortality ratios (SMRs) of 89 and 88 respectively over the full follow up period. For all cancers, the corresponding SMRs were 93 for participants and 92 for controls. Mortality from multiple myeloma was consistent with national rates both for participants and controls, and the relative risk (RR) of myeloma incidence among participants relative to controls was 1.14 (90% CI 0.74 to 1.74) over the full follow up period and 0.79 (90% CI 0.45 to 1.38) during the extended period of follow up (1991–98). Over the full follow up period, leukaemia mortality among participants was consistent with national rates, while rates among controls were significantly lower, and there was a suggestion of a raised risk among test participants relative to controls (RR 1.45, 90% CI 0.96 to 2.17); the corresponding RR for leukaemia incidence was 1.33 (90% CI 0.97 to 1.84). After excluding chronic lymphatic leukaemia (CLL), which is not thought to be radiation inducible, the RR of leukaemia mortality increased to 1.83 (90% CI 1.15 to 2.93), while that for incidence was little changed. Analysis of subgroups of participants with greater potential for exposure provided little evidence of increased risks, although the numbers of men involved were smaller and the statistical power was therefore less. Among other types of cancer, only for liver cancer incidence was there evidence of differences in rates between participants and controls in both the earlier and in the additional period of follow up. Mortality rates among test participants from causes other than cancer were generally similar to those among the controls. Conclusions: Overall levels of mortality and cancer incidence in UK nuclear weapons test participants have continued to be similar to those in a matched control group, and overall mortality has remained lower than expected from national rates. There was no evidence of an increased raised risk of multiple myeloma among test participants in recent years, and the suggestion in the first analysis of this study of a raised myeloma risk is likely to have been a chance finding. There was some evidence of a raised risk of leukaemia other than CLL among test participants relative to controls, particularly in the early years after the tests, although a small risk may have persisted more recently. This could be a chance finding, in view of low rates among the controls and the generally small radiation doses recorded for test participants. However, the possibility that test participation caused a small absolute risk of leukaemia other than CLL cannot be ruled out.

50 Hz magnetic field exposure alters onset of S-phase in normal human fibroblasts.

This study was undertaken to investigate whether power frequency magnetic fields can affect the kinetics of cell cycle progression in exposed human cells. To achieve this, cultures of normal human fibroblasts were synchronised in the G(0) phase of the cell cycle and exposed to 50 Hz magnetic fields at a range of flux densities. Progression through the cycle was monitored by examining the timing of entry into S phase, as characterised by the onset of DNA synthesis. Simultaneous positive controls were exposed to human recombinant fibroblast growth factor to demonstrate that the system was responsive to external stimuli. Exposure to magnetic fields at 20 and 200 microT induced a small but significant increase in the length of the G(1) phase of the cell cycle. However, exposure at higher flux densities of 2 and 20 mT had no significant effect. These results are discussed in relation to weak magnetic field effects on free radical concentration.

Ischemic Heart Disease in Nuclear Workers First Employed at the Mayak Pa in 1948–1972

AbstractFollowing an earlier study of incidence and mortality of ischemic heart disease (IHD) published in 2010, a second analysis has been conducted based on an extended cohort and five additional years of follow-up. The cohort includes 18,763 workers, of whom 25% were females, first employed at the Mayak PA in 1948–1972 and followed up to the end of 2005. Some of these workers were exposed to external gamma rays only, and others were exposed to a mixture of external gamma-rays and internal alpha-particle radiation. A total of 6,134 cases and 2,629 deaths from IHD were identified in the study cohort. A statistically significant increasing trend was found with total external gamma-ray dose in IHD incidence (ERR/Gy 0.099; 95% CI: 0.045–0.153) after adjusting for non-radiation factors. This value reduced slightly when adjusting for internal liver dose. There was no statistically significant increase trend for internal liver dose in IHD incidence. These findings were consistent with an earlier study. New findings in IHD incidence revealed a statistically significant decrease in IHD incidence among workers exposed to external gamma-rays doses of 0.2–0.5 Gy in relation to the external doses below 0.2 Gy. This decreased risk is heavily influenced by female workers. This finding has never been reported in other studies, and the results should be treated with caution. The findings for IHD mortality are similar to those results in the earlier analysis; there was no statistically significant trend with external gamma-ray dose or for internal liver dose after adjustment for external dose. The risk estimates obtained from these analyses of IHD incidence and mortality in relation to external gamma-rays in the cohort of Mayak workers are generally compatible with those from other large occupational radiation worker studies and the Japanese atomic bomb survivors.

Risks of circulatory diseases among Mayak PA workers with radiation doses estimated using the improved Mayak Worker Dosimetry System 2008.

The new Mayak Worker Dosimetry System 2008 (MWDS-2008) was published in 2013 and supersedes the Doses-2005 dosimetry system for Mayak Production Association (PA) workers. It provides revised external and internal dose estimates based on the updated occupational history data. Using MWDS-2008, a cohort of 18,856 workers first employed at one of the main Mayak PA plants during 1948–1972 and followed up to 2005 was identified. Incidence and mortality risks from ischemic heart disease (IHD) (International Classification of Diseases (ICD)-9 codes 410–414) and from cerebrovascular diseases (CVD) (ICD-9 codes 430–438) were examined in this cohort and compared with previously published risk estimates in the same cohort based on the Doses-2005 dosimetry system. Significant associations were observed between doses from external gamma-rays and IHD and CVD incidence and also between internal doses from alpha-radiation and IHD mortality and CVD incidence. The estimates of excess relative risk (ERR)/Gy were consistent with those estimates from the previous studies based on Doses-2005 system apart from the relationship between CVD incidence and internal liver dose where the ERR/Gy based on MWDS-2008 was just over three times higher than the corresponding estimate based on Doses-2005 system. Adjustment for smoking status did not show any effect on the estimates of risk from internal alpha-particle exposure.