Estimation of the risks of ionising radiation.

Probably more is known about the quantitative relationship between exposure and carcinogenesis for radiation than for any other carcinogenic agent. Nevertheless from the brief review given here it is obvious that even for radiation the data are meagre and often not appropriate to the problems of setting dose limits for the protection of radiation workers. ICRP derived a quantitative relationship between exposure and risk of cancer induction and used it to justify their recommended dose limits for exposure. This was done by proposing that the acceptable risk should be about 10(-4) per year. No doubt there will be many other views expressed on acceptable risk which is quite clearly a political issue. If other views prevail and an alternative value is adopted then the dose limit will have to be changed by reference to the dose-risk relationship. This new feature of radiological protection which follows automatically once a quantitative relationship between dose and risk has been recommended, does not seem to be widely recognised. The comparative method of assessing acceptability of actual radiation exposures by comparing cancer mortality data with other industries, does have the advantage that in principle the results of the comparison should be simple and understandable to workers, managers and the public. However, the one analysis of mortality data which is available for a group of radiation workers at Hanford, has lead to a considerable controversy over the method of analysis. The author thinks that the way ahead in radiological protection must lie in the study of cancer morbidity and mortality and not with the theoretical approach where predicted cancer mortality is compared with death rates from industrial accidents, which is the approach used by ICRP in Publication 26.

Chromosome aberrations induced in human lymphocytes by radiation from 252Cf.

In vitro dose--response curves of unstable chromosome aberrations in human lymphocytes have been obtained for 252Cf neutron radiation. The aberration yields fitted best to the linear function Y=aD, which is consistent with the single-track model of aberration formation for high LET radiation. The curves have been compared with others previously produced in this laboratory for several energies of neutrons and for 60Co gamma radiation. The r.b.e. for 252Cf with respect to 60Co is 27 at very low doses, decreasing to 6 at an aberration yield equivalent to 400 rad of 18 rad/hour gamma radiation. A profile of chromosome-aberration induction with depth in a perspex phantom was obtained by placing blood samples at several distances over the range 0.65-2.0 cm from the californium source. This profile was compared with depth-damage calculations for a radium needle. The r.b.e. of 252Cf radiation relative to 226Ra gamma radiation increased with the distance from the source, implying that californium is more effective at greater distances in destroying the ability of cells to divide, which may be an advantage in the treatment of large tumours.

The effect of x-ray induced mitotic delay on chromosome aberration yields in human lymphocytes.

The extent to which X-ray induced mitotic delay at 150 and 400 rad influences chromosome aberration yields was examined in human peripheral blood lymphocytes. The dicentric was used as a marker and aberrations yields were obtained for mixed cultures prepared from equal numbers of normal and irradiated cells. The cultures were terminated following incubation times of 36-120 h. Greater mitotic delay of the order of a few hours was observed at the higher dose. However most reduction in the number of lymphocytes arriving at metaphase by 48 h may be ascribed to interphase death or failure to transform. Analysis of the dicentric distributions which were expected to follow Poisson statistics indicated that cells containing dicentrics were delayed relative to irradiated but aberration-free cells. Cells with one dicentric moved more easily through the first cell cycle than cells containing two dicentrics. Following accidental partial body irradiation, selection in culture favouring the unirradiated lymphocytes does not distort the aberration yield sufficiently to warrant incubation times in excess of the standard 48-52 h.

The observation and analysis of cancer deaths among classified radiation workers.

The extent to which occupational radiation exposure contributes to cancer mortality is an influence on future world energy policy. It is also a factor in deciding the level of expenditure to reduce radiation levels experienced by workers. Here we discuss some of the difficulties in analysing the situation and present the results of some calculations which estimate the expected age-specific radiation mortalities from all inducible cancers and also from leukaemia separately. Using a high value for the average occupational exposure and a conservative estimate of the associated risk, we find that a survey of mortality among radiation workers must run over many years before sufficient data would be accumulated to resolve the effects of radiation-induced neoplasms from those arising from other causes. We show the advisability of determining the cause of death both of persons who remain employed in the industry and all for only a short time. Our estimates are based on maintenance of an occupationally exposed dose of one rad per person per year during the period of the survey which may extend over several decades. However, scaling of the estimates to any other exposure rates is easily performed. We also give estimates of the lowest risk coefficients detectable in a given observation time. Since for a work force of 3000 these lowest detectable values are an order of magnitude larger than those expected, it is clear that only a national or international survey can produce data adequate for even modest objectives.

A comparison of physical and cytogenetic estimates of radiation dose in patients treated with iodine-131 for thyroid carcinoma.

Physical and cytogenetic estimates of the whole-body radiation doses have been compared in 11 patients receiving large doses of iodine-131 for the treatment of thyroid carcinoma. The physical estimate was based on the measurement of thyroid uptake, of the plasma activity variation, and of urinary activity. The cytogenetic estimate was obtained from the analysis of chromosome aberrations in peripheral blood lymphocytes. Good agreement between the estimates was observed in patients whose thyroid glands had previously been ablated by radioiodine. In patients who had varying degrees of thyroid function, there were considerable differences between the estimates with the cytogenetic value always being higher. It is suggested that these differences might be due in part to non-uniform irradiation of lymphocytes by local sources of activity in the thyroid and in the liver.

Chromosome aberrations induced in human lymphocytes by neutron irradiation.

In vitro dose--response curves of unstable chromosome aberrations in human lymphocytes have been obtained for neutron spectra of mean energies 0-7, 0-9, 7-6 and 14-7 MeV. The aberration yields have been fitted to the quadratic function Y = alphaD + betaD2, which is consistent with the single-track and two-track model of aberration formation. However with high-LET radiation, the linear component of yield, corresponding to damage caused by single tracks, predominants, and this term becomes more dominant with increasing LET, so that for fission spectrum neutrons the relationship is linear, Y = alphaD. At low doses, such as those recieved by radiation workers, limiting r.b.e. values between 13 and 47 are obtained relative to 60Co gamma-radiation. At higher doses, as used in radiotherapy, the values are much lower; ranging from 2-7 to 8 at 200 rad of equivalent gamma-radiation. Both sets of r.b.e. values correlate well with track-averaged LET but not with dose-averaged LET. When the numbers of cells without aberrations are plotted against radiation dose, curves are obtained which are similar in shape to those for conventional cell-survival experiments with comparable neutron spectra. The Do values obtained in the present study are close to those from other cell system.

The relationship between chromosome aberrations and low LET radiation dose to human lymphocytes.

In vitro dose-response curves of unstable chromosome aberrations in human lymphocytes have been obtained for 250 kV X-rays and cobalt-60gamma-radiation. The aberration yields have been fitted to the quadratic function Y = alphaD +betaD2, which is consistent with the single-track and two-track model for aberration formation. The values of the coefficients alpha and beta support the hypothesis that the dose-rate effect is limited to the D2 term. The main difference between the coefficients for X- and gamma-radiation is in the alpha values, indicating that X-rays are slightly more efficient, at lower doses, in producing two lesions with a single ionizing track. The lower limits of dose estimate, with 500 cells analysed, are 4 rad for X-rays and 10 rad gamma-radiation. Further evidence is presented confirming that, for cytogenetic dosimetry, in vitro dose-response curves should be prepared by irradiating whole blood maintained at 37 degrees C and prior to PHA stimulation. Curves were plotted showing the variation of the number of cells without aberrations with radiation dose and the shape of these curves were compared with those from human cell survival experiments.

An investigation of the characteristics of a negative pion beam by means of induced chromosome aberration in human peripheral blood lymphocytes.

The depth dose profiles of unstable chromosome aberrations were determined by irradiating blood samples at various depths in a plastic phantom exposed to a beam of negative pi mesons (pions). The pions were derived from an experimental beam line from the Nimrod 7 GeV proton synchrotron. With a momentum of 160 MeV/c and a spread of 15 per cent a Bragg profile was produced peaking at 13-9 cm. An ionization peak to plateau ratio of 1-6 was obtained and for cytogenetic damage this was increased to 2-9. Dicentric and acentric dose-response data from peak and plateau positions were fitted to Y=alphaD+betaD-2 models for comparison with data obtained from 60-Co gamma-rays and fission neutrons. With respect to 150 rads gamma-radiation, the r.b.e. values for the pion peak were 2-1 for dicentrics and 2-3 for acentrics. In the plateau the value for both aberrations was 1-5. At pion doses likely to be used as daily radiotherapy fractions, the aberrations predominantly resulted from single-track events, indicating little likelihood of interfraction recovery, particularly in the peak position. It is concluded that the biological damage characteristics of pion beams, as determined from a cytogenetic end-point, offer several features attractive to the radiotherapist.