Mammography-oncogenecity at low doses.

Controversy exists regarding the biological effectiveness of low energy x-rays used for mammography breast screening. Recent radiobiology studies have provided compelling evidence that these low energy x-rays may be 4.42 +/- 2.02 times more effective in causing mutational damage than higher energy x-rays. These data include a study involving in vitro irradiation of a human cell line using a mammography x-ray source and a high energy source which matches the spectrum of radiation observed in survivors from the Hiroshima atomic bomb. Current radiation risk estimates rely heavily on data from the atomic bomb survivors, and a direct comparison between the diagnostic energies used in the UK breast screening programme and those used for risk estimates can now be made. Evidence highlighting the increase in relative biological effectiveness (RBE) of mammography x-rays to a range of x-ray energies implies that the risks of radiation-induced breast cancers for mammography x-rays are potentially underestimated by a factor of four. A pooled analysis of three measurements gives a maximal RBE (for malignant transformation of human cells in vitro) of 4.02 +/- 0.72 for 29 kVp (peak accelerating voltage) x-rays compared to high energy electrons and higher energy x-rays. For the majority of women in the UK NHS breast screening programme, it is shown that the benefit safely exceeds the risk of possible cancer induction even when this higher biological effectiveness factor is applied. The risk/benefit analysis, however, implies the need for caution for women screened under the age of 50, and particularly for those with a family history (and therefore a likely genetic susceptibility) of breast cancer. In vitro radiobiological data are generally acquired at high doses, and there are different extrapolation mechanisms to the low doses seen clinically. Recent low dose in vitro data have indicated a potential suppressive effect at very low dose rates and doses. Whilst mammography is a low dose exposure, it is not a low dose rate examination, and protraction of dose should not be confused with fractionation. Although there is potential for a suppressive effect at low doses, recent epidemiological data, and several international radiation risk assessments, continue to promote the linear no-threshold (LNT) model. Finally, recent studies have shown that magnetic resonance imaging (MRI) is more sensitive than mammography in detecting invasive breast cancer in women with a genetic sensitivity. Since an increase in the risk associated with mammographic screening would blur the justification of exposure for this high risk subgroup, the use of other (non-ionising) screening modalities is preferable.

Dose distribution measurements and calculations for Dounreay hot particles.

Discrete fragments of irradiated nuclear fuel have been discovered on the foreshore at the Dounreay nuclear site in Scotland, offshore on the seabed and at nearby beaches which have public access. The fragments contain mainly (137)Cs and (90)Sr/(90)Y and for particles recovered to date, (137)Cs activities are within the range of 10(3) to 10(8) Bq. The most active particles found at Sandside Beach contain approximately 3 x 10(5)Bq (137)Cs. Direct measurements of the spatial dose distributions from 37 fuel fragments were measured in detail for the first time using radiochromic dye film as part of a national evaluation of the associated potential radiological hazard. Monte Carlo code calculations of the doses are in good agreement with measurements, taking into account variations to be expected due to differences in shape and the increasing importance of self-absorption for the larger, more active fragments. Dose measurements provide little evidence for wide variations in the (137)Cs:(90)Sr/(90)Y ratio between fragments. Specific attention is given to the evaluation of skin dose, averaged over an area of 1 cm(2) at a depth of 0.07 mm, since this is of major radiological concern. There is no obvious dependence of skin dose on the site of origin of the fragments (foreshore, seabed or beaches) for a given (137)Cs activity level. A dose rate survey instrument (SmartION) was shown to provide a rapid and convenient method for skin dose assessment from fuel fragments in the (137)Cs activity range measured (2 x 10(5) to 2 x 10(7) Bq). A conversion factor multiplier of 240 can be applied to the open window SmartION scale reading to estimate the skin dose rate within +/-25%.

Comparison of measured and calculated spatial dose distributions for a bench-mark 106Ru/106Rh hot particle source.

This study is a part of a programme of research to provide validated dose measurement and calculation techniques for beta emitting hot particles by the construction of well-defined model hot particle sources. This enables parallel measurements and calculations to be critically compared. This particular study concentrates on the high-energy beta emitter, (106)Ru/(106)Rh (Emax = 3.54 MeV). This source is a common constituent of failed nuclear fuel, particularly in accident situations. The depth dose distributions were measured using radiochromic dye film (RDF); an imaging photon detector coupled to an LiF thermoluminescent dosemeter (LiF-IPD) and an extrapolation ionisation chamber (ECH). Dose calculations were performed using the Monte Carlo radiation transport code MCNP4C. Doses were measured and calculated as average values over various areas and depths. Of particular interest are the doses at depths of 7 and 30-50 mg cm(-2), and averaged over an area of 1 cm2, as recommended by the International Commission on Radiological Protection for use in routine and accidental over-exposures of the skin. In this case, the average ratios (MCNP/measurement) for RDF, ECH and LiF-IPD were 1.07 +/- 0.02, 1.02 +/- 0.01 and 0.83 +/- 0.16, respectively. There are significantly greater discrepancies between the ECH and LiF-IPD measurement techniques and calculations-particularly for shallow depths and small averaging areas.

Hot particle dosimetry and radiobiology--past and present.

Small high-activity radioactive particles of nominal diameter ranging from approximately 1 mm down to several microm have been a radiological concern over the last 30 years in and around European and American nuclear reactor facilities. These particles have often been referred to as 'hot particles'. The 'hot particle problem' came into prominent concern in the late 1960s. The potential carcinogenic effects in lungs as the result of irradiation by discrete small particles containing alpha-emitting radionuclides, particularly (239)Pu, were claimed by some to be several orders of magnitude greater than those produced by uniform irradiation to the same mean dose. The phrase 'hot particle problem' was subsequently used to refer to the difficulty of predicting health effects for all microscopic radioactive sources. The difficulty arose because of the paucity of comparative human, animal or cell studies using radioactive particles, and the lack of validated measurement or calculational techniques for dose estimation for non-uniform exposures. Experience was largely restricted to uniform, large-area/volume exposures. The concern regarding cancer induction was extended to deterministic effects when the ICRP in 1977 failed to give adequate dose limits for dealing with 'hot particle' exposures of the skin. Since 1980, considerable efforts have been made to clarify and solve the dosimetric and radiobiological issues related to the health effects of 'hot particle' exposures. The general recommendations of the ICRP in 1991 used the latest radiobiological data to provide skin dose limits which are applicable to 'hot particle' exposures. More recently the NCRP has extended considerations to other organs. This progress is reviewed and applied to the specific case of the recent evaluation of potential health effects of Dounreay fuel fragments commissioned by the Scottish Environment Protection Agency (SEPA). Analyses of possible doses and risks in this case indicate that the principal concern following skin contact, ingestion or inhalation is the possibility of localised ulceration of skin or of the mucosal lining of the colon or extra-thoracic airways.

Radon exposure of the skin: I. Biological effects.

Radon progeny can plate out on skin and give rise to exposure of the superficial epidermis from alpha emitters Po-218 (7.7 MeV, range approximately 66 microm) and Po-214 (6 MeV, range approximately 44 microm). Dose rates from beta/gamma emitters Pb-214 and Bi-214 are low and only predominate at depths in excess of the alpha range. This paper reviews the evidence for a causal link between exposure from radon and its progeny, and deterministic and stochastic biological effects in human skin. Radiation induced skin effects such as ulceration and dermal atrophy, which require irradiation of the dermis, are ruled out for alpha irradiation from radon progeny because the target cells are considerably deeper than the range of alpha particles. They have not been observed in man or animals. Effects such as erythema and acute epidermal necrosis have been observed in a few cases of very high dose alpha particle exposures in man and after acute high dose exposure in animals from low energy beta radiations with similar depth doses to radon progeny. The required skin surface absorbed doses are in excess of 100 Gy. Such effects would require extremely high levels of radon progeny. They would involve quite exceptional circumstances, way outside the normal range of radon exposures in man. There is no definitive identification of the target cells for skin cancer induction in animals or man. The stem cells in the basal layer which maintain the epidermis are the most plausible contenders for target cells. The majority of these cells are near the end of the range of radon progeny alpha particles, even on the thinnest body sites. The nominal depth of these cells, as recommended by the International Commission on Radiological Protection (ICRP), is 70 microm. There is evidence however that some irradiation of the hair follicles and/or the deeper dermis, as well as the inter-follicular epidermis, is also necessary for skin cancer induction. Alpha irradiation of rodent skin that is restricted to the epidermis does not produce skin cancer. Accelerator generated high energy helium and heavy ions can produce skin cancer in rodents at high doses, but only if they penetrate deep into the dermis. The risk figures for radiation induced skin cancer in man recommended by the ICRP in 1990 are based largely on x and beta irradiated cohorts, but few data exist below absorbed doses of about 1 Gy. The only plausible finding of alpha-radiation induced skin cancer in man is restricted to one study in Czech uranium miners. There is no evidence in other uranium miners and the Czech study has a number of shortcomings. This review concludes that the overall balance of evidence is against causality of radon progeny exposure and skin cancer induction. Of particular relevance is the finding in animal studies that radiation exposure of cells which are deeper than the inter-follicular epidermis is necessary to elicit skin cancer. In spite of this conclusion, a follow-on paper evaluates the attributable risk of radon to skin cancer in the UK on the basis that target cells for skin cancer induction are the cells in the basal layer of the inter-follicular epidermis-since this is the conservative assumption made by international bodies such as the International Commission on Radiological Protection (ICRP) for general radiological protection purposes.

Radon exposure of the skin: II. Estimation of the attributable risk for skin cancer incidence.

A preceding companion paper has reviewed the various factors which form the chain of assumptions that are necessary to support a suggested link between radon exposure and skin cancer in man. Overall, the balance of evidence was considered to be against a causal link between radon exposure and skin cancer. One factor against causality is evidence, particularly from animal studies, that some exposure of the hair follicles and/or the deeper dermis, as well as the inter-follicular epidermis, is required-beyond the range of naturally occurring alpha particles. On this basis any skin cancer risk due to radon progeny would be due only to beta and gamma components of equivalent dose, which are 10-100 times less than the alpha equivalent dose to the basal layer. Notwithstanding this conclusion against causality, calculations have been carried out of attributable risk (ATR, the proportion of cases occurring in the total population which can be explained by radon exposure) on the conservative basis that the target cells are, as is often assumed, in the basal layer of the epidermis. An excess relative risk figure is used which is based on variance weighting of the data sources. This is 2.5 times lower than the value generally used. A latent period of 20 years and an RBE of 10 are considered more justifiable than the often used values of 10 years and 20 respectively. These assumptions lead to an ATR of approximately 0.7% (0.5-5%) at the nominal UK indoor radon level of 20 Bq m(-3). The range reflects uncertainties in plate-out. Previous higher estimates by various authors have made more pessimistic assumptions. There are some indications that radon progeny plate-out may be elevated out of doors, particularly due to rainfall. Although average UK outdoor radon levels ( approximately 4 Bq m(-3)) are much less than average indoor levels, and outdoor residence time is on average about 10%, this might have the effect of increasing the ATR several-fold. This needs considerable further study. Ecological epidemiology data for the South West of England provide no evidence for elevated skin cancer risks at radon levels <100 Bq m(-3). Case-control or cohort studies would be necessary to address the issue authoritatively.

LNT--an apparent rather than a real controversy?

Can the carcinogenic risks of radiation that are observed at high doses be extrapolated to low doses? This question has been debated through the whole professional life of the author--now nearing four decades. In its extreme form the question relates to a particular hypothesis (LNT) used widely by the international community for radiological protection applications. The linear no-threshold (LNT) hypothesis propounds that the extrapolation is linear and that it extends down to zero dose. The debate on the validity of LNT has increased dramatically in recent years. This is in no small part due to concern that exaggerated risks at low doses leads to undue amounts of societal resources being used to reduce man-made human exposure and because of the related growing public aversion to diagnostic and therapeutic medical exposures. The debate appears to be entering a new phase. There is a growing realisation of the limitations of fundamental data and the scientific approach to address this question at low doses. There also appears to be an increasing awareness that the assumptions necessary for a workable and acceptable system of radiological protection at low doses must necessarily be based on considerable pragmatism. Recent developments are reviewed and a historical perspective is given on the general nature of controversies in radiation protection over the years. All the protagonists in the debate will at the end of the day probably be able to claim that they were right!

Enhanced biological effectiveness of low energy X-rays and implications for the UK breast screening programme.

Recent radiobiological studies have provided compelling evidence that the low energy X-rays as used in mammography are approximately four times--but possibly as much as six times--more effective in causing mutational damage than higher energy X-rays. Since current radiation risk estimates are based on the effects of high energy gamma radiation, this implies that the risks of radiation-induced breast cancers for mammography X-rays are underestimated by the same factor. The balance of risk and benefit for breast screening have been re-analysed for relative biological effectiveness (RBE) values between 1 and 6 for mammography X-rays. Also considered in the analysis is a change in the dose and dose-rate effectiveness factor (DDREF) from 2 to 1, women with larger than average breasts and implications for women with a family history of breast cancer. A potential increase in RBE to 6 and the adoption of a DDREF of unity does not have any impact on the breast screening programme for women aged 50-70 years screened on a 3 yearly basis. Situations for which breast screening is not justified due to the potential cancers induced relative to those detected (the detection-to-induction ratio (DIR)) are given for a range of RBE and DDREF values. It is concluded that great caution is needed if a programme of early regular screening with X-rays is to be used for women with a family history of breast cancer since DIR values are below 10 (the lowest value considered acceptable for women below 40 years) even for modest increases in the RBE for mammography X-rays.

The skin in radiological protection--recent advances and residual unresolved issues.

Exposure of the skin is important in radiological protection because, as the most superficial organ of the body, it can often receive the highest absorbed dose from an external exposure. It also has the highest radiation-induced cancer incidence risk factor of any organ (although mortality is very low). The ICRP and NCRP have, particularly over the past 15 y, been able to set dose limits for the exposure of the skin on the basis of an extensive body of radiobiological, clinical and epidemiological data. Some of the main advances in skin dose limitation in radiological protection and some of the remaining unresolved issues are reviewed.

Development of an ICCD-scintillator system for measurement of spatial dose distributions around 'hot particles'.

An intensified charge coupled device (ICCD)-scintillator system has been investigated for potential use in measuring the spatially non-uniform dose distribution around 'hot particles'. This imaging system is capable of producing real-time measurements considerably quicker than other presently available radiation dosimetry techniques and exhibits good linearity and reproducibility and relatively high spatial resolution (approximately 17.5 microm). The time required for a dose evaluation is less than a hundredth that required for radiochromic dye film measurements. The non-uniformity of the system has been eliminated by applying pixel-to-pixel correction factors. The measurable dose rate range using a 110 microm thick scintillator extends from approximately 2000 down to approximately 6 Gy h(-1). The prototype ICCD-scintillator system has been used in evaluation of the skin dose from some high-activity nuclear fuel fragments. The results agree within a few percentage with radiochromic dye film measurements for 1 cm(2) averaging areas.

Doses and risks from the ingestion of Dounreay fuel fragments.

The radiological implications of ingestion of nuclear fuel fragments present in the marine environment around Dounreay have been reassessed by using the Monte Carlo code MCNP to obtain improved estimates of the doses to target cells in the walls of the lower large intestine resulting from the passage of a fragment. The approach takes account of the reduction in dose due to attenuation within the intestinal wall and self-absorption of radiation in the fuel fragment itself. In addition, dose is calculated on the basis of a realistic estimate of the anatomical volume of the lumen, rather than being based on the average mass of the contents, as in the current ICRP model. Our best estimates of doses from the ingestion of the largest Dounreay particles are at least a factor of 30 lower than those predicted using the current ICRP model. The new ICRP model will address the issues raised here and provide improved estimates of dose.

Electron spectra measurements and Monte Carlo calculations for a 60Co standardised hot particle source.

A benchmark set of measured beta particle spectra for a standardised 60Co hot particle source is presented. The spectra were obtained for conditions similar to those encountered in practical dosimetric applications. The measured spectra were compared with Monte Carlo calculations using the MCNP code. These comparisons provided information to guide the selection of the optimal set-up parameters of the code. Important differences were observed in the MCNP calculated spectra when ITS and the default indexing style algorithm were used. Overall the calculations using the default mode of MCNP version 4B provide the best agreement with the measured electron spectra.

Carcinogenic risk of hot-particle exposures.

It has been suggested that spatially non-uniform radiation exposures, such as those from small radioactive particles ('hot particles'), may be very much more carcinogenic than when the same amount of energy is deposited uniformly throughout a tissue volume. This review provides a brief summary of in vivo and in vitro experimental findings, and human epidemiology data, which can be used to evaluate the veracity of this suggestion. Overall, this supports the contrary view and indicates that average dose, as advocated by the ICRP, is likely to provide a reasonable estimate of carcinogenic risk (within a factor of approximately +/- 3). There are few human data with which to address this issue. The limited data on lung cancer mortality following occupational inhalation of plutonium aerosols, and the incidence of liver cancer and leukaemia due to thorotrast administration for clinical diagnosis, do not appear to support a significant enhancement factor. Very few animal studies, including mainly lung and skin exposures, provide any indication of a hot-particle enhancement for carcinogenicity. Some recent in vitro malignant transformation experiments provide evidence foran enhanced cell transformation for hot-particle exposures but, properly interpreted, the effect is modest. Few studies extend below absorbed doses of approximately 0.1 Gy.

Experimental simulation of A-bomb gamma ray spectra for radiobiology studies.

Improved radiation protection of humans requires a better understanding of the mechanisms of radiation action and accurate estimates of radiation risk for both internal and external radiations. The Japanese atomic bomb survivors represent one of the most important sources of human data on the late carcinogenic effects of ionising radiations. The present study was undertaken to investigate whether it would be possible to use hospital radiotherapy/radiobiology equipment to mimic the spectra encountered in Hiroshima and Nagasaki. The estimated total gamma ray fluence spectra (including both prompt and delayed photons) at both Hiroshima and Nagasaki, for distances of 500, 1000, 1500 and 2000 m have been evaluated using DS86 data and previously unpublished information for delayed gamma radiations which constitute the major contribution to survivor doses. Monte Carlo (EGS4) simulations were performed to transport these photons through the body in order to investigate the variation in electron spectra for various body organs. The electron spectra obtained for these fluences at, for example, the colon, have been matched with combinations of electron spectra produced by linear accelerators to within 5% SD. These will, for the first time, enable a direct link to be made between radiobiological studies (for example, on mammography spectra) and the epidemiological data from Japan, which currently underpin radiation risk estimates.

A wide dynamic range, high-spatial-resolution scanning system for radiochromic dye films.

This paper describes the evaluation of an inexpensive, commercially available 35 mm transparency slide scanner as a potential alternative scanning device for GafChromic HD-810 radiochromic dye film. Besides its low cost, the principal advantages of this type of scanner are high spatial resolution and high speed (a typical scan taking less than 1 min). With broad-band illumination the useful dose range using grey-scale imaging of GafChromic HD-810 is limited to about 50-800 Gy. By using the colour-scale imaging capability of the scanner we have been able to achieve a significant extension covering a similar range (15-2000 Gy) to that attainable using monochromatic illumination. The short-term reproducibility of the system is good, with a coefficient of variation of doses estimated from repeat scanning of uniformly exposed calibration films of less than 2%. Long-term stability is ensured by the scanning of a manufacturer-supplied test slide. The slide scanner system has been used in the determination of depth dose distributions from a model 'hot particle' source containing 106Ru/Rh. GafChromic dye film stacks irradiated by the source were read out on both the slide scanner and a conventional Joyce Loebl MDM6 scanning stage microdensitometer. The overall agreement between the dose estimates provided by the two systems was within 10%.

The measurement of thermal neutron flux depression for determining the concentration of boron in blood.

Boron neutron capture therapy (BNCT) is a form of targeted radiotherapy that relies on the uptake of the capture element boron by the volume to be treated. The treatment procedure requires the measurement of boron in the patient's blood. The investigation of a simple and inexpensive method for determining the concentration of the capture element 10B in blood is described here. This method, neutron flux depression measurement, involves the determination of the flux depression of thermal neutrons as they pass through a boron-containing sample. It is shown via Monte Carlo calculations and experimental verification that, for a maximum count rate of 1 x 10(4) counts/s measured by the detector, a 10 ppm 10B sample of volume 20 ml can be measured with a statistical precision of 10% in 32 +/- 2 min. For a source activity of less than 1.11 x 10(11) Bq and a maximum count rate of less than 1 x 10(4) counts/s, a 10 ppm 10B sample of volume 20 ml can be measured with a statistical precision of 10% in 58 +/- 3 min. It has also been shown that this technique can be applied to the measurement of the concentration of any element with a high thermal neutron cross section such as 157Gd.

Time- and dose-related changes in the thickness of skin in the pig after irradiation with single doses of thulium-170 beta particles.

Time-related changes in skin thickness have been evaluated in the pig using a noninvasive ultrasound technique after exposure to a range of single doses of 0.97 MeV beta particles from (170)Tm plaques. The reduction in relative skin thickness developed in two phases; the separation into two phases was statistically justified only after 120 Gy (P = 0.04). The first phase was between 12 weeks and 24 weeks after irradiation. No further changes were seen until 48-60 weeks after irradiation, when a second phase of skin thinning was observed. No further changes in relative skin thickness were seen in the follow-up period of 104 weeks. The timing of these phases of relative skin thinning was totally independent of the radiation dose; however, the severity of each phase of radiation-induced skin thinning was related to the dose. The pattern of changes was similar to that reported previously after irradiation with 2.27 MeV beta particles from (90)Sr/(90)Y, but the degree of dermal thinning was less for a similar skin surface dose. From a comparison of the depth-dose distribution of the beta particles from the two radionuclides, it was concluded that the target cell population responsible for both the first and second phase of skin thinning in pig skin after irradiation may be located at approximately 800 microm depth. This corresponds to an area in the reticular dermis in pig skin and may be the appropriate site at which to measure the average dose to the dermal tissue.