1976, British Journal of Radiology, 49, 191-193
FEBRUARY
1976
Proceedings of The British Institute of Radiology Abstracts of papers read at the Radiobiology Work-in-Progress meeting held on Friday, October 17,1975, in the Reid-Knox Hall, Institute House, 32 Welbeck Street, London W1M 7PG* The radiation sensitivity of Dictyostelium discoideum, by N. E. Gillies and N. Hariratnajothi. Inactivation and mutation of cultured mammalian cells by radiations of different LET, by J. Thacker and R. Cox. Problems in using neutron beams to test the theory of "oxygen production in the track", by Shirley Hornsey and T. Alper. Monte Carlo methods for analysing the accuracy of survival-curve parameters, by N. M. Blackett and O. C. A. Scott. Effects of radiation and hyperthermia on an in vitro tumour model, by R. E. Durand. Renal function in the rat following irradiation, as monitored with a gamma-camera, by F. R. Hudson, B. M. Chauser and M. L. Law. Tolerance of pig kidney to fractionated X-irradiation, by J. Hopewell and R. J. Berry.
THE RADIATION SENSITIVITY OF DICTYOSTELIUM DISCOIDEUM"
PROBLEMS IN USING NEUTRON BEAMS TO TEST THE THEORY OF "OXYGEN PRODUCTION IN THE TRACK"
By N. E. Gillies and N. Hariratnajothi
By Shirley Hornsey and T. Alper
Department of Biology as Applied to Medicine The Middlesex Hospital Medical School London W1P 6DB The effect of y rays and ultraviolet light (UV) on the viability of unaggregated cells of the slime mould Dictyostelium discoideum was examined. It was found that during the first 30—40 hours after the beginning of germination of the spores with bacteria on an agar surface, the cells became progressively more sensitive to y rays. Sensitivity to UV was constant for the first ten hours after the beginning of germination, but it decreased sharply between ten hours and 20 hours, becoming constant at a new level after that time. The appearance of increased resistance to UV inactivation may represent the synthesis of an enzyme system capable of dealing with some of the UV damage, but without effect in reducing the expression of y-ray damage. It is suggested that the increasing sensitivity to y rays may be caused by lack of time to repair lesions during the initial period of growth after irradiation.
M.R.C. Cyclotron Unit Hammersmith Hospital, London W12 0HS and Gray Vernon Hospital Northwood, Middlesex HA6 2RN If the formation of oxygen (or a similarly acting species) in the tracks of heavily ionizing particles is a valid explanation for reduction in oxygen enhancement ratios (OER) with increasing LET, it follows that measured values of K should be higher at high than at low LET (Neary, 1965). The difference in K values should equal the equivalent concentration of oxygen produced in the high LET track. Support for the oxygen-in-the-track hypothesis came from K-value measurements using Shigella flexneri as test organism (Alper, Moore and Bewley, 1967)and also from particle beam experiments using tests independent of the measurement of K values (Alper and Moore, 1967; Alper and Bryant, 1974). However, Howard, Gilbert and Green (1974), using the alga Oedogonium, and Hendry, Gilbert and Howard (1974), who made observations on colony formation by mouse bone marrow cells, failed to find that the K value "for neutrons" was greater than for X rays. Cullen (personal communication) has likewise found no difference in K values for cultured mouse ascites tumour cells with X rays and fast neutrons. The apparent disagreement can be explained by an examination of the OERs for the different secondary charged particles produced in the neutron beam. These can be considered in two groups, the very densely ionizing a and heavy recoil particles and the less densely ionizing knock-on protons. For mammalian cells in culture Bewley, McNally and Page (1974) and Broerse, Barendsen and Van Kersen (1968) showed that the OER for the a and heavy recoils was 1. The RBE for these particles was high, so, although the a and heavy recoils gave only 20 per cent of the physical dose they were responsible for about 50 per cent of the biological damage. The OER for the neutron beam as a whole is therefore very dependent on the relative RBE values for the a plus heavy recoils and for the knock-on protons. With Shigella the RBE for the heavy recoil particles is probably less than 1 so they are responsible for less than 20 per cent of the biological effect. This explains the difference in the gain factor (OER X rays/OER neutrons) observed for entero-bacteria and mammalian cells (Alper and Moore, 1967). Where the OER for the a's and heavy recoils is 1, the K value for the neutron beam will reflect the K value for the proton component in the dose only; a maximal estimate of the average [O2] in the track from these particles is 1 /xM and this would be too small to be detected as a difference in K values for any test system for which the K value was more than about 5 /xM.
INACTIVATION AND MUTATION OF CULTURED MAMMALIAN CELLS BY RADIATIONS OF DIFFERENT LET
By J. Thacker and R. Cox M.R.C. Radiobiology Unit Harwell, Didcot, Oxon. 0X11 ORD Induced mutation frequencies can be measured in irradiated mammalian cell cultures by selecting cells which have acquired resistance to the cytotoxic purine analogue 6-thioguanine. These mutants are deficient in the purine salvage enzyme hypoxanthine-guanine phosphoribosyl transferase (HGPRT). We have recently established for both human diploid cells and V79 Chinese hamster cells that a simple relationship exists between radiation-induced inactivation and the induction of HGPRT-deficient mutants. Despite differences in the radio-sensitivity of the two cell types, plots of induced mutation frequency versus log surviving fraction show the same linear relationship for both types. Radiations of low LET were used in these experiments, but preliminary data are now available for radiations with LETs in the range 50-200 keV fim.-1. The similarity of the mutation-survival relationships for the two cell types persists with these radiations, but the relationship may depart from linearity at low surviving fractions with radiations of LET exceeding 100 keVjimr1. For both cell types, the maximum RBE for the induction of HGPRT-deficient mutants is approximately twice that found for inactivation. *Reprints available from the Editorial Office.
191
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49, No. 578 Proceedings of The British Institute of Radiology
Neutron beams are therefore unsuitable sources of high LET radiation to test Neary's hypothesis, but the results which have been obtained with them are not inconsistent with the hypothesis.
confidence limits given by the program. This demonstrates the need for external evidence that the two N values are the same before the program can be used correctly. The method described can be applied to a wide variety of problems without requiring a detailed mathematical knowledge of statistics.
REFERENCES ALPER, T., and BRYANT, P., 1974. Reduction in oxygen
advancement ratio with increase in LET: Tests of two hypotheses. International Journal of Radiation Biology, .29,3,203-218. ALPER, T., and MOORE, J. L., 1967. The interdependence of
oxygen enhancement ratios for 250 kVp X rays and fast neutrons. British Journal of Radiology, 40, 843-848.
EFFECTS OF RADIATION AND HYPERTHERMIA ON AN "IN VITRO" TUMOUR MODEL
By R. E. Durand
University of Wisconsin as a determinant of bacterial radiosensitivity and its Madison, U.S.A. modification by anoxia and glycerol. Radiation Research, Hyperthermia has recently received attention as a potential 32, 277-293. anti-cancer agent, due in part to preliminary observations BEWLEY, D. K., MCNALLY, N. J., and PAGE, B. C , 1974. hypoxic cells may be more thermosensitive than wellEffects of secondary charged-particle spectrum on that oxygenated cells. Histological observations of heat-treated cellular response to fast neutrons. Radiation Research, multicell "spheroids", in in vitro tumour models which dis55,111-121. play central hypoxia and necrosis similar to that observed BROERSE, J. J., BARENDSEN, G. W., and VAN KERSEN, G. R., in many nodular tumours in vivo, tend to support this sugges1968. Survival of cultured human cells after irradiation tion. However, quantitative hyperthermic studies of the with fast neutrons of different energies in hypoxic and viability of individual cells from the hypoxic and welloxygenated conditions. International Journal of Radiation oxygenated regions of spheroids have not proved as Biology, 13, 559-572. optimistic. HENDRY, J. H., GILBERT, C. W., and HOWARD, Alma, 1975. thermo-resistance of cells grown as small spheroids K values and gain factors for fast neutrons and X-rays is The increased above that of single cells, analogous to the for mammalian cell cystems (CFU) in vivo. Radiation enhanced radioresistance previously observed under these Research, 61, 504-512. growth conditions. A further increase in thermo-resistance HOWARD, Alma, GILBERT, C. W., and GREEN, D., 1974. been noted for larger spheroids, apparently due to the Dependence of radiation sensitivity on oxygen tension in has of non-cycling, heat-resistant cells. In still Oedogonium. III. Applicability of Howard-Flanders- accumulation spheroids, the development of hypoxic cells does not, Alper formula for 14 MeV neutron irradiation. Radiation larger however, lead to appreciable thermal sensitivity. Thus, the Botany, 14, 4, 353-356. hyperthermic killing of spheroid cells is qualitatively similar NEARY, G. J., 1965. Chromosome observations and the to killing by radiation. theory of RBE. I. General considerations. International Heat can, however, be effectively used as an adjuvant to Journal of Radiation Biology, 9, 477-502. radiation. The synergistic interaction between the modalities is well known, but a further potentiation has been observed in the spheroid system. The latter effect is apparently due to changes in metabolic activity of heated cells—that is, the respiration (oxygen consumption) of cells is inhibited at MONTE CARLO METHODS FOR ANALYSING THE temperatures greater than 42°C, leading to greater peneACCURACY OF SURVIVAL-CURVE PARAMETERS tration of oxygen into the spheroid with a concomitant By N. M. Blackett and O. C. A. Scott increase in net cellular radiosensitivity. Thus, hyperthermia indirectly potentiates the response of the previously hypoxic Institute of Cancer Research cells. This may account, at least in part, for the apparent Royal Marsden Hospital enhancement of hypoxic-cell-killing by combined treatment Sutton, Surrey SM2 5PX with heat and radiation. A means for investigating the accuracy of estimates of radiobiological parameters is described, which makes use of a computer to generate hypothetical survival-curve data (using random numbers) based on defined values of Do and N. This data can be used to obtain estimates of Do and N by RENAL FUNCTION IN THE RAT FOLLOWING whatever method of curve fitting is desired. Repetition of this process many times gives the mean estimated value and IRRADIATION AS MONITORED WITH A GAMMA-CAMERA its standard deviation. Different sources of experimental By F. R. Hudson, B. M. Chauser and M. P. Law variation can be introduced that may conform to different Medical Physics Department andM.R.C. Cyclotron Unit distributions thus allowing one to depart from standard Hammersmith Hospital, London statistical assumptions such as normally distributed errors and independence of individual measurements. Effective renal plasma flow (ERPF) in the rat 123 was measured The possibility of introducing bias into the estimates of by monitoring the uptake and clearance of I-hippuran, radiobiological parameters and the size of the standard using a gamma-camera coupled to a computer for data error can be compared for different curve fitting procedures processing. A pinhole collimator was employed to give for circumstances closely resembling those obtained in clearly-defined images which were used to estimate plasma practice. Application of this method to the Pike-Alper pro- flow to each kidney. Normal values of total ERPF in the gram for determining dose modifying factors confirms that a rat were found to be 2-9 ml./minute/100 g body weight. The considerable improvement in the accuracy of the estimate technique has been used to monitor the effects of single of the Do ratio is obtained provided the N values for the doses of 1,000, 2,000, and 3,000 rads 250 kVp X rays on a single kidney. Major renal failure was observed 18 weeks two curves are the same. However if the N values are not the same the method after 2,000 rads and slightly earlier after 3,000 rads. Renal introduces a systematic bias into the estimate of the Do failure may be related with the development offibrosisand ratio so that the true ratio can be outside the 95 per cent collagen deposition. The collagen content of each kidney was ALPER, T., MOORE, J. L., and BEWLEY, D. K., 1967. LET
192
FEBRUARY
1976
Proceedings of The British Institute of Radiology measured by estimating hydroxyproline, an amino acid which is specific to collagen. It was increased in irradiated kidneys 20 weeks after doses of 2,000 and 3,000 rads. There was a positive correlation between collagen content and loss of kidney function. This was independent of dose suggesting that they may be causally related. TOLERANCE OF PIG KIDNEY TO FRACTIONATED X-IRRADIATION
By J. W. Hopewell and R. J. Berry Research Institute Churchill Hospital, Oxford The effects of X-irradiation on the kidney of the Large White pig has been used as a model for determining time and fractionation factors for predicting renal tolerance. In each animal one kidney was irradiated with one of six fractionation regimes; single doses, 6 or 14 fractions in 18 days and 6, 14 or 30 fractions in 39 days. Renal tolerance was determined by the presence or absence of significant function in the irradiated kidney, as compared with the contralateral unirradiated kidney in the same animal, using 131 I Hippuran renography.
The levels of renal tolerances obtained six months after treatment with the fractionated doses are confirmed by subsequent renograms carried out for periods up to two years after treatment. For kidneys treated daily (14F/18 days or 30F/39 days) with total doses 15 to 30 per cent below tolerance, however, a transient loss of function was observed 18 months after treatment. Function had returned in these animals at two years. Kidney weights obtained when animals were killed supported the levels of tolerance obtained by functional studies. Kidneys with no function weighed less than 30 g while those showing evidence of function had weights in excess of 80 g. The tolerance levels obtained showed that renal tolerance could not be predicted by a simple mathematical formula. The fractions exponent was found to vary with the overall treatment time (0-24 for 6 and 14 fractions in 18 days and 0-49 for 6, 14 and 30 fractions in 39 days) as did the "time exponent for a fixed number of fractions (0-11 for 6 fractions given between 18 and 39 days and 0-38 for 14 fractions given over the same time period). The levels of renal tolerance determined in the pig correlated well with accepted levels of tolerance used in clinical practice.
Book reviews MRC Report 1975: Criteria for controlling radiation doses to the public after accidental escape of radioactive material, pp. vii+48,1975 (H.M.S.O.), £1 -30. Previous MRC Reports (1959-61) have also dealt with this topic, but new metabolic and dosimetric data made available over the past 14 years have enabled revised and more comprehensive calculations to be made of the levels of radiation dose that warrant remedial action in the event of the accidental escape of radioactive materials into the environment. While the ICRP have recommended criteria for regulating "controllable" exposures, it is appropriate that the MRC should provide criteria for "uncontrolled sources" since these would specifically refer to social conditions in the United Kingdom. The Council have revised their emergency reference levels of dose (ERLs) for various body tissues and the data used and methods of calculation are given in the appendices of the report. The report also discusses the release of radionuclides that could occur when an operating reactor is involved in an accident and concludes that in addition to 89Sr, 90Sr, isotopes of iodine, 132 Te and 137 Cs, other nuclides such as 242Cm, 95Zr, 106Ru, 140Ba, and 144Ce might also be of importance as far as internal radiation doses are concerned. The intention of the report is to give guidance to all who are concerned with plans for the public in the event of a release of radioactive material. It recommends that there should be a "single standing body" namely the National Radiological Protection Board to advise on the interpretation and application of the general principles discussed in the report. The report deals in detail with ERLs for isotopes of iodine, 137 Cs, 89Sr and 90Sr in air and milk and pasture and those for insoluble particles in lung. Although as stated the report is intended for those who might be engaged in taking counter-measures to reduce the radiation exposure to individuals or populations it will also be of scientific interest to all who are engaged in radiation protection. In addition it contains useful dosimetric data.
Radiology in Primary Care. 17 authors, Edited by Glenn V. Dalrymple and John E. Slayden, pp. 330, 1975 (Saint Louis, The C.V. Mosby Co., distributed in Britain by Henry Kimpton), £11 25. This book is directed toward the primary physician in training and practice, says the Preface. You might innocently suppose that it would therefore aim at teaching clinicians how to make best use of their X-ray departments and radiologists. In fact, this book is for those in medical practice who want to set up their own X-ray suite alongside their consulting-room, with hardly a radiologist in sight. The volume is concise and remarkably comprehensive, taking in the basic physics of X-ray production and absorption, design of the X-ray room, equipment, radiation protection and biology. The bulk of the book describes and illustrates the basic radiographic projections, including exposure factors, with simple examples of abnormal radiographs. As it is meant for general practice, its longest chapter is rightly that on orthopaedics. Intravenous urograms and cholecystograms are discussed in detail, but the do-it-yourself approach stops short of special examinations like barium meals. The immediate reaction of radiologist readers could be unprintable, because this is of course heresy, poaching, putting the clock back, etc. Indeed, the pitfalls of amateur radiological practice are lit up by the book's plea that the doctor should engage a qualified radiographer, rather than train his own staff. The implication is that someone unqualified might commonly do the radiography in this setting. At first sight the possible appeal ©f this book in Britain appears rather limited—it is not for the radiologist in training. But whether radiologists can or should cope with the whole burden of X-ray services is now under discussion here (see "Must radiologists do all the reporting", B.J.R., July, 1975, p. 517). If general practitioners interested in radiology come to look after an X-ray room in the small community hospital, this book would make a very good primer for them.
T. H. E. BRYANT.
193
T.
SHERWOOD.
FEBRUARY
1976
Proceedings of The British Institute of Radiology Abstracts of papers read at the Radiobiology Work-in-Progress meeting held on Friday, October 17,1975, in the Reid-Knox Hall, Institute House, 32 Welbeck Street, London W1M 7PG* The radiation sensitivity of Dictyostelium discoideum, by N. E. Gillies and N. Hariratnajothi. Inactivation and mutation of cultured mammalian cells by radiations of different LET, by J. Thacker and R. Cox. Problems in using neutron beams to test the theory of "oxygen production in the track", by Shirley Hornsey and T. Alper. Monte Carlo methods for analysing the accuracy of survival-curve parameters, by N. M. Blackett and O. C. A. Scott. Effects of radiation and hyperthermia on an in vitro tumour model, by R. E. Durand. Renal function in the rat following irradiation, as monitored with a gamma-camera, by F. R. Hudson, B. M. Chauser and M. L. Law. Tolerance of pig kidney to fractionated X-irradiation, by J. Hopewell and R. J. Berry.
THE RADIATION SENSITIVITY OF DICTYOSTELIUM DISCOIDEUM"
PROBLEMS IN USING NEUTRON BEAMS TO TEST THE THEORY OF "OXYGEN PRODUCTION IN THE TRACK"
By N. E. Gillies and N. Hariratnajothi
By Shirley Hornsey and T. Alper
Department of Biology as Applied to Medicine The Middlesex Hospital Medical School London W1P 6DB The effect of y rays and ultraviolet light (UV) on the viability of unaggregated cells of the slime mould Dictyostelium discoideum was examined. It was found that during the first 30—40 hours after the beginning of germination of the spores with bacteria on an agar surface, the cells became progressively more sensitive to y rays. Sensitivity to UV was constant for the first ten hours after the beginning of germination, but it decreased sharply between ten hours and 20 hours, becoming constant at a new level after that time. The appearance of increased resistance to UV inactivation may represent the synthesis of an enzyme system capable of dealing with some of the UV damage, but without effect in reducing the expression of y-ray damage. It is suggested that the increasing sensitivity to y rays may be caused by lack of time to repair lesions during the initial period of growth after irradiation.
M.R.C. Cyclotron Unit Hammersmith Hospital, London W12 0HS and Gray Vernon Hospital Northwood, Middlesex HA6 2RN If the formation of oxygen (or a similarly acting species) in the tracks of heavily ionizing particles is a valid explanation for reduction in oxygen enhancement ratios (OER) with increasing LET, it follows that measured values of K should be higher at high than at low LET (Neary, 1965). The difference in K values should equal the equivalent concentration of oxygen produced in the high LET track. Support for the oxygen-in-the-track hypothesis came from K-value measurements using Shigella flexneri as test organism (Alper, Moore and Bewley, 1967)and also from particle beam experiments using tests independent of the measurement of K values (Alper and Moore, 1967; Alper and Bryant, 1974). However, Howard, Gilbert and Green (1974), using the alga Oedogonium, and Hendry, Gilbert and Howard (1974), who made observations on colony formation by mouse bone marrow cells, failed to find that the K value "for neutrons" was greater than for X rays. Cullen (personal communication) has likewise found no difference in K values for cultured mouse ascites tumour cells with X rays and fast neutrons. The apparent disagreement can be explained by an examination of the OERs for the different secondary charged particles produced in the neutron beam. These can be considered in two groups, the very densely ionizing a and heavy recoil particles and the less densely ionizing knock-on protons. For mammalian cells in culture Bewley, McNally and Page (1974) and Broerse, Barendsen and Van Kersen (1968) showed that the OER for the a and heavy recoils was 1. The RBE for these particles was high, so, although the a and heavy recoils gave only 20 per cent of the physical dose they were responsible for about 50 per cent of the biological damage. The OER for the neutron beam as a whole is therefore very dependent on the relative RBE values for the a plus heavy recoils and for the knock-on protons. With Shigella the RBE for the heavy recoil particles is probably less than 1 so they are responsible for less than 20 per cent of the biological effect. This explains the difference in the gain factor (OER X rays/OER neutrons) observed for entero-bacteria and mammalian cells (Alper and Moore, 1967). Where the OER for the a's and heavy recoils is 1, the K value for the neutron beam will reflect the K value for the proton component in the dose only; a maximal estimate of the average [O2] in the track from these particles is 1 /xM and this would be too small to be detected as a difference in K values for any test system for which the K value was more than about 5 /xM.
INACTIVATION AND MUTATION OF CULTURED MAMMALIAN CELLS BY RADIATIONS OF DIFFERENT LET
By J. Thacker and R. Cox M.R.C. Radiobiology Unit Harwell, Didcot, Oxon. 0X11 ORD Induced mutation frequencies can be measured in irradiated mammalian cell cultures by selecting cells which have acquired resistance to the cytotoxic purine analogue 6-thioguanine. These mutants are deficient in the purine salvage enzyme hypoxanthine-guanine phosphoribosyl transferase (HGPRT). We have recently established for both human diploid cells and V79 Chinese hamster cells that a simple relationship exists between radiation-induced inactivation and the induction of HGPRT-deficient mutants. Despite differences in the radio-sensitivity of the two cell types, plots of induced mutation frequency versus log surviving fraction show the same linear relationship for both types. Radiations of low LET were used in these experiments, but preliminary data are now available for radiations with LETs in the range 50-200 keV fim.-1. The similarity of the mutation-survival relationships for the two cell types persists with these radiations, but the relationship may depart from linearity at low surviving fractions with radiations of LET exceeding 100 keVjimr1. For both cell types, the maximum RBE for the induction of HGPRT-deficient mutants is approximately twice that found for inactivation. *Reprints available from the Editorial Office.
191
VOL.
49, No. 578 Proceedings of The British Institute of Radiology
Neutron beams are therefore unsuitable sources of high LET radiation to test Neary's hypothesis, but the results which have been obtained with them are not inconsistent with the hypothesis.
confidence limits given by the program. This demonstrates the need for external evidence that the two N values are the same before the program can be used correctly. The method described can be applied to a wide variety of problems without requiring a detailed mathematical knowledge of statistics.
REFERENCES ALPER, T., and BRYANT, P., 1974. Reduction in oxygen
advancement ratio with increase in LET: Tests of two hypotheses. International Journal of Radiation Biology, .29,3,203-218. ALPER, T., and MOORE, J. L., 1967. The interdependence of
oxygen enhancement ratios for 250 kVp X rays and fast neutrons. British Journal of Radiology, 40, 843-848.
EFFECTS OF RADIATION AND HYPERTHERMIA ON AN "IN VITRO" TUMOUR MODEL
By R. E. Durand
University of Wisconsin as a determinant of bacterial radiosensitivity and its Madison, U.S.A. modification by anoxia and glycerol. Radiation Research, Hyperthermia has recently received attention as a potential 32, 277-293. anti-cancer agent, due in part to preliminary observations BEWLEY, D. K., MCNALLY, N. J., and PAGE, B. C , 1974. hypoxic cells may be more thermosensitive than wellEffects of secondary charged-particle spectrum on that oxygenated cells. Histological observations of heat-treated cellular response to fast neutrons. Radiation Research, multicell "spheroids", in in vitro tumour models which dis55,111-121. play central hypoxia and necrosis similar to that observed BROERSE, J. J., BARENDSEN, G. W., and VAN KERSEN, G. R., in many nodular tumours in vivo, tend to support this sugges1968. Survival of cultured human cells after irradiation tion. However, quantitative hyperthermic studies of the with fast neutrons of different energies in hypoxic and viability of individual cells from the hypoxic and welloxygenated conditions. International Journal of Radiation oxygenated regions of spheroids have not proved as Biology, 13, 559-572. optimistic. HENDRY, J. H., GILBERT, C. W., and HOWARD, Alma, 1975. thermo-resistance of cells grown as small spheroids K values and gain factors for fast neutrons and X-rays is The increased above that of single cells, analogous to the for mammalian cell cystems (CFU) in vivo. Radiation enhanced radioresistance previously observed under these Research, 61, 504-512. growth conditions. A further increase in thermo-resistance HOWARD, Alma, GILBERT, C. W., and GREEN, D., 1974. been noted for larger spheroids, apparently due to the Dependence of radiation sensitivity on oxygen tension in has of non-cycling, heat-resistant cells. In still Oedogonium. III. Applicability of Howard-Flanders- accumulation spheroids, the development of hypoxic cells does not, Alper formula for 14 MeV neutron irradiation. Radiation larger however, lead to appreciable thermal sensitivity. Thus, the Botany, 14, 4, 353-356. hyperthermic killing of spheroid cells is qualitatively similar NEARY, G. J., 1965. Chromosome observations and the to killing by radiation. theory of RBE. I. General considerations. International Heat can, however, be effectively used as an adjuvant to Journal of Radiation Biology, 9, 477-502. radiation. The synergistic interaction between the modalities is well known, but a further potentiation has been observed in the spheroid system. The latter effect is apparently due to changes in metabolic activity of heated cells—that is, the respiration (oxygen consumption) of cells is inhibited at MONTE CARLO METHODS FOR ANALYSING THE temperatures greater than 42°C, leading to greater peneACCURACY OF SURVIVAL-CURVE PARAMETERS tration of oxygen into the spheroid with a concomitant By N. M. Blackett and O. C. A. Scott increase in net cellular radiosensitivity. Thus, hyperthermia indirectly potentiates the response of the previously hypoxic Institute of Cancer Research cells. This may account, at least in part, for the apparent Royal Marsden Hospital enhancement of hypoxic-cell-killing by combined treatment Sutton, Surrey SM2 5PX with heat and radiation. A means for investigating the accuracy of estimates of radiobiological parameters is described, which makes use of a computer to generate hypothetical survival-curve data (using random numbers) based on defined values of Do and N. This data can be used to obtain estimates of Do and N by RENAL FUNCTION IN THE RAT FOLLOWING whatever method of curve fitting is desired. Repetition of this process many times gives the mean estimated value and IRRADIATION AS MONITORED WITH A GAMMA-CAMERA its standard deviation. Different sources of experimental By F. R. Hudson, B. M. Chauser and M. P. Law variation can be introduced that may conform to different Medical Physics Department andM.R.C. Cyclotron Unit distributions thus allowing one to depart from standard Hammersmith Hospital, London statistical assumptions such as normally distributed errors and independence of individual measurements. Effective renal plasma flow (ERPF) in the rat 123 was measured The possibility of introducing bias into the estimates of by monitoring the uptake and clearance of I-hippuran, radiobiological parameters and the size of the standard using a gamma-camera coupled to a computer for data error can be compared for different curve fitting procedures processing. A pinhole collimator was employed to give for circumstances closely resembling those obtained in clearly-defined images which were used to estimate plasma practice. Application of this method to the Pike-Alper pro- flow to each kidney. Normal values of total ERPF in the gram for determining dose modifying factors confirms that a rat were found to be 2-9 ml./minute/100 g body weight. The considerable improvement in the accuracy of the estimate technique has been used to monitor the effects of single of the Do ratio is obtained provided the N values for the doses of 1,000, 2,000, and 3,000 rads 250 kVp X rays on a single kidney. Major renal failure was observed 18 weeks two curves are the same. However if the N values are not the same the method after 2,000 rads and slightly earlier after 3,000 rads. Renal introduces a systematic bias into the estimate of the Do failure may be related with the development offibrosisand ratio so that the true ratio can be outside the 95 per cent collagen deposition. The collagen content of each kidney was ALPER, T., MOORE, J. L., and BEWLEY, D. K., 1967. LET
192
FEBRUARY
1976
Proceedings of The British Institute of Radiology measured by estimating hydroxyproline, an amino acid which is specific to collagen. It was increased in irradiated kidneys 20 weeks after doses of 2,000 and 3,000 rads. There was a positive correlation between collagen content and loss of kidney function. This was independent of dose suggesting that they may be causally related. TOLERANCE OF PIG KIDNEY TO FRACTIONATED X-IRRADIATION
By J. W. Hopewell and R. J. Berry Research Institute Churchill Hospital, Oxford The effects of X-irradiation on the kidney of the Large White pig has been used as a model for determining time and fractionation factors for predicting renal tolerance. In each animal one kidney was irradiated with one of six fractionation regimes; single doses, 6 or 14 fractions in 18 days and 6, 14 or 30 fractions in 39 days. Renal tolerance was determined by the presence or absence of significant function in the irradiated kidney, as compared with the contralateral unirradiated kidney in the same animal, using 131 I Hippuran renography.
The levels of renal tolerances obtained six months after treatment with the fractionated doses are confirmed by subsequent renograms carried out for periods up to two years after treatment. For kidneys treated daily (14F/18 days or 30F/39 days) with total doses 15 to 30 per cent below tolerance, however, a transient loss of function was observed 18 months after treatment. Function had returned in these animals at two years. Kidney weights obtained when animals were killed supported the levels of tolerance obtained by functional studies. Kidneys with no function weighed less than 30 g while those showing evidence of function had weights in excess of 80 g. The tolerance levels obtained showed that renal tolerance could not be predicted by a simple mathematical formula. The fractions exponent was found to vary with the overall treatment time (0-24 for 6 and 14 fractions in 18 days and 0-49 for 6, 14 and 30 fractions in 39 days) as did the "time exponent for a fixed number of fractions (0-11 for 6 fractions given between 18 and 39 days and 0-38 for 14 fractions given over the same time period). The levels of renal tolerance determined in the pig correlated well with accepted levels of tolerance used in clinical practice.
Book reviews MRC Report 1975: Criteria for controlling radiation doses to the public after accidental escape of radioactive material, pp. vii+48,1975 (H.M.S.O.), £1 -30. Previous MRC Reports (1959-61) have also dealt with this topic, but new metabolic and dosimetric data made available over the past 14 years have enabled revised and more comprehensive calculations to be made of the levels of radiation dose that warrant remedial action in the event of the accidental escape of radioactive materials into the environment. While the ICRP have recommended criteria for regulating "controllable" exposures, it is appropriate that the MRC should provide criteria for "uncontrolled sources" since these would specifically refer to social conditions in the United Kingdom. The Council have revised their emergency reference levels of dose (ERLs) for various body tissues and the data used and methods of calculation are given in the appendices of the report. The report also discusses the release of radionuclides that could occur when an operating reactor is involved in an accident and concludes that in addition to 89Sr, 90Sr, isotopes of iodine, 132 Te and 137 Cs, other nuclides such as 242Cm, 95Zr, 106Ru, 140Ba, and 144Ce might also be of importance as far as internal radiation doses are concerned. The intention of the report is to give guidance to all who are concerned with plans for the public in the event of a release of radioactive material. It recommends that there should be a "single standing body" namely the National Radiological Protection Board to advise on the interpretation and application of the general principles discussed in the report. The report deals in detail with ERLs for isotopes of iodine, 137 Cs, 89Sr and 90Sr in air and milk and pasture and those for insoluble particles in lung. Although as stated the report is intended for those who might be engaged in taking counter-measures to reduce the radiation exposure to individuals or populations it will also be of scientific interest to all who are engaged in radiation protection. In addition it contains useful dosimetric data.
Radiology in Primary Care. 17 authors, Edited by Glenn V. Dalrymple and John E. Slayden, pp. 330, 1975 (Saint Louis, The C.V. Mosby Co., distributed in Britain by Henry Kimpton), £11 25. This book is directed toward the primary physician in training and practice, says the Preface. You might innocently suppose that it would therefore aim at teaching clinicians how to make best use of their X-ray departments and radiologists. In fact, this book is for those in medical practice who want to set up their own X-ray suite alongside their consulting-room, with hardly a radiologist in sight. The volume is concise and remarkably comprehensive, taking in the basic physics of X-ray production and absorption, design of the X-ray room, equipment, radiation protection and biology. The bulk of the book describes and illustrates the basic radiographic projections, including exposure factors, with simple examples of abnormal radiographs. As it is meant for general practice, its longest chapter is rightly that on orthopaedics. Intravenous urograms and cholecystograms are discussed in detail, but the do-it-yourself approach stops short of special examinations like barium meals. The immediate reaction of radiologist readers could be unprintable, because this is of course heresy, poaching, putting the clock back, etc. Indeed, the pitfalls of amateur radiological practice are lit up by the book's plea that the doctor should engage a qualified radiographer, rather than train his own staff. The implication is that someone unqualified might commonly do the radiography in this setting. At first sight the possible appeal ©f this book in Britain appears rather limited—it is not for the radiologist in training. But whether radiologists can or should cope with the whole burden of X-ray services is now under discussion here (see "Must radiologists do all the reporting", B.J.R., July, 1975, p. 517). If general practitioners interested in radiology come to look after an X-ray room in the small community hospital, this book would make a very good primer for them.
T. H. E. BRYANT.
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