Patricia J. Lindop

LONG-TERM EFFECTS OF A SINGLE WHOLE-BODY EXPOSURE OF MICE TO IONIZING RADIATIONS. II. CAUSES OF DEATH

The causes of death in mice exposed at the age of 30 days to a single whole-body dose of 15 MeV X-rays have been analyzed from the point of view of both percentage incidence and distribution in time. Ten groups of death causes were used, based on post-mortem findings. In the lower dose groups (50 to 457 r), the percentage incidence was found, in most cases, to vary very little with dose, but some diseases, e. g. leukaemia, did show a definite increase, and others, e. g. pulmonary tumours, a definite decrease with increasing dose. The changes in incidence were linearly related to the dose. The analysis of survival curves for each cause of death separately has revealed that while all causes were advanced by radiation, some were advanced more than others. A definite correlation was found between the acceleration of a given cause of death and the rate of change of the percentage incidence with dose. This suggests that the change of incidence is merely the result of the changed times of onset of disease; an actuarial correction has confirmed this suggestion. It is concluded that the probability of any one disease occurring remains the same in irradiated as in the control animals, the main effect of the radiation being an advancement, at different rates, of all causes of death. The age of the animal at irradiation may be an important factor in determining the relative acceleration of the different diseases. In the high dose groups (549 to 780 r) a definite decrease in incidence of neoplastic diseases has been established. This may be due to a 4 radiotherapeutic’ effect in cells which later in life might have become manifest as neoplasms.

Long-Term Effects of a Single Whole-Body Exposure of Mice to Ionizing Radiations. I. Life-Shortening

A systematic study has been made of the reduction of life span in mice exposed to a single whole-body dose of 15 MeV X-rays. 4604 mice of an inbred A substrain were used, all of the same age, 30 days, when irradiated. Nine dose groups, from 50 to 780 r, were used, with a large number of control mice, which were kept to the end of their lives under the same conditions as the irradiated animals. An analysis of the survival curves has revealed two effects of radiation: a reduction in the median age and an increase in standard deviation of the distribution of ages at death. The latter was found to be a quadratic function of dose and it is suggested that the increase is the result of the larger spread in the ages of onset of diseases in irradiated animals. The reduction of life span was found to be proportional to dose, with no threshold. It amounts to 5∙66 ± 0∙18 weeks per 100 r, or to 38 % of the median life span for a dose equal to the LD50 (698 r). The difference between the life-shortening in males and females was not statistically significant. The data have also been analyzed in terms of Gompertz plots and it was found that they cannot be represented by straight lines, although the displacement of the curves caused by radiation is roughly proportional to dose. The fact that after correcting for the change in standard deviation, all survival curves are parallel to each other, suggests that the effect of exposure is to ‘age the animal, by the removal of a few weeks of its early life.

Oxygen cathode measurements in the mouse testis

Gold oxygen cathodes, calibrated against a Hersch cell, have been used to monitor oxygen concentrations in the mouse testis. The technique of calibration of the electrodes is described, together with measurements made in mice breathing gas mixtures with different oxygen contents, from 5 to 100%. Mice were found to survive for at least four minutes breathing these mixtures, and the level of tissue hypoxia produced when breathing 10 or 5% oxygen is lower than can be achieved by breathing pure nitrogen. The results show that an oxygen parameter, with dimen- sions of oxygen concentration, may be measured with relatively large electrodes, and is related directly to variations in alveolar pO2.

Radiation Response of HeLa Cells Exposed at Very Low Temperatures

SummaryHeLa—S—3 cells have been irradiated with 14 MeV electrons in single doses, at temperatures from 310°K down to 77°K. The best plating efficiency resulted from cooling the cells at 1°K/min in the presence of 15 per cent glycerol, and then plunging into the refrigerant, and rapid thawing post-irradiation. Over the temperature range studied the D0 of the cell survival curve increased three-fold at the change of state, i.e. the freezing point, then increased at about 0·8 rad per °K. The extrapolation number was increased three-fold at 77°K, but hypoxia did not further modify the D0 or extrapolation number at this temperature.

A REMOTE-CONTROL APPARATUS FOR IRRADIATION OF MICE AND RATS.

An apparatus is described which enables 48 mice to be irradiated in batches of four, each container with animals being brought consecutively into the irradiation area by remote control. The apparatus also enables one to control the gas breathed by the animals during irradiation, its rate of flow and temperature.

Induction of lung tumours by the action of radiation and urethane.

IN a recent paper, Foley and Cole1 reported some investigations of the incidence of lung tumours in mice exposed to different doses of X-rays, followed by an injection of urethane. They assumed that the lung tumours are induced by the urethane and that the X-rays have an inhibitory effect on the tumour incidence. On this basis they interpreted their results as showing a dependence of this inhibitory action on radiation dose with a threshold of about 300 rads.

The Effect of Hypoxia on Radiation Life-shortening in Drosophila Melanogaster

SummaryRadiation-induced life-shortening in Drosophila melanogaster has been measured. Flies were irradiated at a dose-rate of 1430 rads/sec whilst breathing various mixtures of oxygen and nitrogen. Neither a detectable age dependence nor a sex difference was noted. There was no difference in sensitivity with oxygen contents of 6–21 per cent; under 100 per cent nitrogen, life-shortening was reduced. This difference in sensitivity was due to an increase in the plateau region at low doses for nitrogen. For higher doses inactivation constants for both sets of curves were similar Thus the o.e.r. was dependent on the level of damage. For the acute effects of radiation there was no protection under nitrogen. This study is relevant to the effects of radiation on post-mitotic normal tissue.

Prospective life-science payloads

A viable spacelab programme is based on the thesis that biomedical specialists require a quantifiable, and possibly mechanistic, understanding of the significant changes observed in crew, in and after manned space flights. Only then can prophylaxis or atraumatic reversal be achieved (with potentially an added use to ameliorate qualitatively similar disease aspects on Earth). This approach could justify national funding to promote lead-up ground-based research as well as research and development for special equipment, of which the spin-off into clinical practice could well precede its first use in Spacelab. The requirement for applied expediency arises from the watershed met early in the evolution of a life-sciences programme. Initially, the facility of space flight provoked numerous valid experiments designed to test for, or quantitate, gravity-dependent mechanisms and their interaction with other agents, radiation, vibration, or absence of triggers for rhythmic patterns. In parallel, measurable parameters of mans function in space were being monitored, primarily to promote survival by remedial action when available. Monitoring data were then developed to find a critical mechanism feasible to testing. Often the rationale for such tests and experiments was that man was there and could, moreover, attend to several biological experiments in space! The watershed appeared when man in a Spacelab was shown as a hazard to the instrumentation, cleanliness, accuracy, thermal control, weight limits, etc. essential to the other disciplines. Other than the life sciences only the technological requirements of materials processing required a manned spacelab! So, life scientists have needed to rethink their payloads, and their constrictions, to plan for compatible load sharing. A composite of proposed biomedical projects related to apparently unanswered etiology of observed changes in returning astronauts will be used to illustrate the evolution of and possible answers to sample problems. The principles outlined, their moderation by expediency (with the untouched upon need for the enthusiastic involvement of biomedical potential in space projects) should remain our guidelines. This is in spite of the expected obsolescence of these specific projects within the next decade.

Biological Effects of Ionizing Radiations

The Initial Effects of Ionizing Radiations on CellsA Symposium held in Moscow, October, 1960, supported by UNESCO and the IAEA, and sponsored by the Academy of Sciences of the U.S.S.R. Edited by R. J. C. Harris. Pp. xii + 367. (London: Academic Press, Inc. (London), Ltd.; New York: Academic Press, Inc., 1961.) 75s.