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The evidence relating to pre-natal radiation exposure and the subsequent occurrence of malformations and cancer suggests that the overall risk lies in the range 0--1 cases per 1000 irradiated by one rad in utero in the first four months of pregnancy. The natural level of occurrence of serious handicaps in average pregnancies is at least 30 times higher. Is the much lower probability of radiation-induced harm sufficiently high to justify (a) concern when a woman who has been irradiated is found to have been pregnant at that time, or (b) the maintenance of restrictions on medical uses of ionizing radiation in women in the reproductive age, such as the ten day rule?

Acute myeloid leukaemia induction by X- and gamma-rays in 4 mouse strains follows the same dose-response aD2e-lambda D. The (dose)2 interaction disappears within 3 days. AML appears earlier when syngeneic marrow cells are injected 3 days after irradiation, minimum latent period and final frequency remaining unchanged. Dose-responses for brief and protracted exposures are quite different for non-myeloid 'leukemia'. The results seem incompatible with a common model for initiation of both leukaemia categories and with orthodox concepts that initiation is a stable state and must be followed by multiple events over a period of time before cells express fully malignant behaviour.

The form of the dose-response for induction of malignant diseases in vivo by ionizing radiation is not yet established in spite of its scientific interest and its practical importance. Considerably extended observations have confirmed that the dose-response for acute myeloid leukaemia induced in male CBA/H mice by X-ray exposure is highly curvilinear. The dose-response was well fitted by the expression aD2e-lambda D (D = dose) in agreement with induction at the cellular level in proportion to D2 over the whole dose range 0.25-6.0 Gy. The factor e-lambda D accounts for the inescapable concomitant inactivating action of the inducing irradiation. The quantitative aspects of induction of myeloid leukaemia by ionizing radiation are unlike the induction of genetic mutation or cell inactivation and suggest that interaction of two adjoining cells is an essential element in radiation leukaemogenesis.

Cancer is naturally very common, and practical questions about the possibility of radiation-induced harm are often questions about what in other contexts would be called background noise. Central to the question of whether small radiation exposures are carcinogenic is the effect of antenatal radiography. A comparison of singleton and twin births with radiography rates of 10 and 55 per cent respectively showed that radiography must be the main cause of the elevated frequency of malignant disease. In Japanese bomb survivors, most radiation-induced cancer has been found in those irradiated in adult life, less in those irradiated in childhood and adolescence, and least for exposure in utero. Specific biological differences between different kinds of malignant disease in their induction by ionizing radiation are becoming increasingly evident. When dose-response relationships for observed cancer frequencies are to be used as evidence about dose-response relationships for cancer induction, it will always be necessary to allow for the concomitant cell sterilization. When this is done, there is little support for linearity as the method of extrapolation when making predictions about possible effects of low doses but the absence of threshold seems scientifically inescapable. In cellular terms, radiation induction of cancer must be a very rare phenomenon, so rare compared with cell sterilization or mutation induction, that the general corpus of radiobiological understanding may be inapplicable.

Skin reaction to X-irradiation has been studied in the albino guinea-pig; early response in limited-field irradiations of the flank is comparable to that commonly seen in rodents, swine and man, and is dose-dependent with a dynamic range from mild erythema to moist desquamation. The peak early skin reaction is seen between 14 and 21 days after irradiation, and declines before 30 days except at the highest doses used. Fractionation of the X-ray dose at 24 hours results in a 'sparing' of about 340 rad. Permanent partial epilation is detectable at doses in excess of 1400 rad, and complete epilation at 1 year occurs in 50 per cent of irradiated fields at 1740 rad. Twenty-four hour two-dose fractionation results in a 'sparing' of about 500 rad for epilation. Palpable dermal 'fibrosis' is detectable at 3 months after irradiation in fields given more than 2070 rad, and at 1 year after irradiation in fields given more than 1800 rad; 50 per cent of fields showed palpable 'fibrosis' at 1 year at 1930 rad. Unlike domestic swine and man, skin fields in the guinea-pig showed no dimensional contraction after X-ray doses which produced gross early skin damage.

The dose-response for leukaemia induction by exposure to ionizing radiation protracted over several weeks was largely independent of dose not only in X-rayed patients with ankylosing spondylitis but also in experimentally gamma-rayed CBA/H mice. In the experiment the induced leukaemia frequency of acute myeloid leukaemia was independent of a several thousand-fold variation in physical dose rate. Any difference in leukaemia induction between brief and protracted exposures must therefore depend on specifically biological consequences of protracted exposures. Experimental analysis is required to provide the guides for inference about risks of low level exposure from observations on relatively heavily irradiated populations.

Cancer can be induced by radiation in any tissue where cancer occurs naturally. The observation that antenatal diagnostic radiography causes a small but definit increas in childhood cancer is as good evidence as could be expected in support of the scientific expectation that there would be no threshold of dose for carcinogenesis. A linear relation between radiation dose and frequency of of induced cancer is a necessary assumption for a system of radiological protection but is not necessarily a reasonable basis for realistic assessments of cancer risk. Indeed there are radiobiological and epidemiological reasons to the contrary. If the linear hypothesis is accepted then at the present time in the UK the routine practice of medicine is of about 2 orders of magnitude more important in causing cancer than environmental pollution by discharge of radio-activity. The acceptability of radiation safety standards for occupational exposure may be justified by comparison of radiation cancer risks with risks from fatal accidents in the safer industries. The acceptability of the corresponding standards for members of the public seems to require more public discussion of the concept of negligible risk. Emotional reactions to uncontrolled releases of radio-activity are based at least in part on a failure to appreciate the hypothesis of linearity.

Low birthweight infants were given calcium enriched in 46Ca in a single feed. The specific activity of successive urine samples showed that the absorption of the marker was largely complete in about 4 hours. The rate of decrease of urinary specific activity after 3 1/2 hours was exponential and very similar in 8 sets of observations in 6 infants. Its extrapolation backwards to 1 hour may indicate the size of the exchangeable calcium pool, usually about 200 mg/kg body weight. Completeness of faecal collection for estimation of 46Ca is essential for accurate determination of true absorption and endogenous faecal excretion of natural Ca. In 5 infants examined, nor marker was detectable in faeces excreted later than 48 hours after the first stool containing marker. Nevertheless, reasons are given why a collection period limited to 48 hours may sometimes involve error.

In vivo growth characteristics of myeloid leukaemia induced by whole-body irradiation of CBA/H male mice were examined in the strain of origin by procedures expected to enhance or depress immunological responses. Syngeneic growth in vivo (survival time and frequency of takes) was not modified by attempted active immunization with radiation-inactivated cells or by sublethal whole-body irradiation of recipients before inoculation of small numbers of clonogenic cells. Since the growth stimuli involved in in vivo repair of severely damaged normal haemopoietic tissue also did not modify the growth of the radiation-induced leukaemia cells in syngeneic passage, their growth in vivo in the irradiated primary hosts can be regarded as autonomous by the stage at which leukaemia was diagnosed. Challenge inocula in the "immunization" experiments were 1-9 clonogenic cells from 4 different passaged lines and in the whole-body radiation experiments, 1-10(3) clonogenic cells derived from 11 different primary hosts and 4 different passaged lines.