E.V. Hulse

Incidence of Radiation-induced Skin Tumours in Mice and Variations with Dose Rate

Mice were exposed to weakly penetrating beta-particles from an external source, using 12 different surface doses ranging from 5.4 to 260 Gy and given at four different dose rates from 200 to 1.7 cGy/min. As in previous investigations, both epidermal and dermal tumours occurred with the latter predominating. The lowest surface dose to produce a statistically significant increase in skin tumours was 21.7 Gy, no effect being detected with doses of 5.4-16.3 Gy. The dose-response curves rose steeply when obvious increases occurred. Consideration of these findings and the fact that radiation-induced skin tumours can have an exceptionally long latent period leads to the suggestion that there is some relatively radioresistant factor which normally restrains potential radiation-induced cancer cells in the skin from becoming tumours until the skin is subjected to high local doses. Tumour-induction was unaffected by reducing the highest dose rate by a factor of 10 and the dose-response curves were almost identical. Further reductions of dose rate, encompassing a further factor of 10, in general resulted in fewer tumours.

Dose-response models for the radiation-induction of skin tumours in mice

Extensive data on radiation-induced skin tumours in mice were examined using 8 models, all based on the concept that incidences of radiation-induced tumours depend on a combination of two radiation effects: a tumour induction process and the loss of reproductive integrity by the potential tumour cells. Models with and without a threshold were used, in spite of theoretical objections to threshold models. No model fitted well both the epidermal and the dermal tumour data and models which proved to be statistically satisfactory for some of the data were rejected for biological reasons. It is concluded that, for skin tumours, dose-response curves depending on a combination of cancer induction and loss of cellular reproductive integrity are distorted by some special, relatively radio-resistant, factor which we have previously postulated as being involved in radiation skin carcinogenesis.

Radiosensitivities of Cells from Which Radiation-induced Skin Tumours Are Derived

SummaryThe observed incidence of epidermal and dermal tumours in mice following superficial external beta-irradiation may be accounted for by assuming that tumour induction is proportional to the square of the dose and that potential tumour cells lose their reproductive integrity according to a type C cell survival curve. n = 1·2 and D37 = 2440 rads for potential tumour cells of the epidermis and n = 1·9 and D37 = 2280 rads for potential tumour cells of the dermis.

Gastric Emptying in Rats after Part-body Irradiation

SummaryThe effects of part-body x-irradiation on gastric emptying were studied in rats, mainly using a dose of 100 r. Irradiating the head and shoulders did not delay gastric emptying. Irradiating the abdomen delayed emptying as much as whole-body irradiation, but the delay after irradiation of the cranial, caudal, dorsal or ventral halves of the abdomen was less. The cranial half of the abdomen was more sensitive than the caudal half. The right side of the body was as sensitive as the whole body but the left side was less sensitive. Irradiation of a small part of the abdomen through a 1 in. lateral port delayed emptying only slightly less than whole-body irradiation.Anatomical studies led to the conclusion that irradiation of the small intestine and associated structures is the most important factor in producing the delay. Possible mechanisms whereby intestinal irradiation could delay gastric emptying are discussed.

Osteosarcomas, fibrosarcomas and basal-cell carcinomas in rabbits after irradiation with gamma-rays or fission neutrons: an interim report on incidence, site of tumours and RBE.

SummaryOsteosarcomas, fibrosarcomas and basal-cell carcinomas developed after whole-body neutron- or gamma-irradiation of rabbits, appearing sooner after neutron-than gamma-irradiation. Interim data suggest that the RBE for the production of all three types of malignant tumour combined is about 3.Nearly all the osteosarcomas were in the jaw, as in rabbits given 90Sr. However, doses of only 1000–1600 rads of gamma-rays were required, much less than the accumulated dose reported for the corresponding 90Sr-induced osteosarcomas.

RADIATION-CONDITIONED AVERSION IN RATS AFTER PART-BODY X-IRRADIATION AND ITS RELATIONSHIP TO GASTRIC EMPTYING.

SummaryRats irradiated shortly after eating a barium meal may refuse to eat a second barium meal when tested 4 to 6 weeks later. Irradiation of the abdomen was about 60 per cent as effective as whole-body irradiation in producing this aversion, but irradiation of the head and shoulders was only 20 per cent as effective. Irradiation of parts of the abdomen readily produced aversions, but irradiation of the pelvis did not.The strength of the aversion was closely correlated to the severity of the radiation-induced delay in gastric emptying which was observed when the initial barium meal was given, and it is concluded that gastric delay is normally the prime cause of the aversions. The few exceptions suggest that a further, possibly humoral, factor may also be involved when extra-abdominal tissues are irradiated.

The RBE of gamma-rays and fission neutrons for acute and sub-acute effects in irradiated rabbits.

SummaryRabbits were given acute whole-body irradiation with either neutrons (mean energy 0·7 mev, dose range 400–1500 rads) or gamma-rays (mean energy 2·5 mev, dose range 1000–3000 R). The last acute death was at 32 days and the LD50/32 was 572 rads for neutrons and 1389 R for gamma-rays, giving an RBE of 2·4.Acute deaths were primarily due to haemopoietic failure, but damage to the alimentary tract probably also played a part. Coprophagia (re-ingestion), which is normal in rabbits, may have increased the liability to post-irradiation infection.Sub-acute lesions, between 2 and 7 months after irradiation, occurred only after exposure to neutrons and not after gamma-rays. Just over half were local lesions of limbs, related to the entry dose of neutrons, and the remainder were intrathoracic effusions. When these sub-acute effects were taken into account the RBE rose to 3·0.

The Relative Biological Efficiency of Fast Neutrons and Gamma-rays for Life-shortening in Chronically Irradiated CBA Mice

SummaryCBA mice have been irradiated from early maturity to death with low daily doses of fast neutrons or gamma-radiation delivered nearly continuously. For life-shortening the rbe of the fast neutrons was about 10 for mice of either sex; there was no significant dependence on size of daily dose within the range investigated.

The Acute Toxic Effects of Cysteamine and Their Modification by X-irradiation

SummaryThe toxic effects of cysteamine in mice are described. A dose of just over twice the usual radioprotective dose caused severe convulsions and killed about half the injected animals. The dangers of using this compound in man are discussed.When a toxic dose of cysteamine was followed by 100 rads of x-rays 2–15 min later, there was a statistically significant reduction in the number of deaths caused by the cysteamine. Doses of 500–5000 rads had no effect on cysteamine mortality. Possible mechanisms are discussed, and a radiation effect on the nervous system is thought to be more likely than a reversal of the protective effect of cysteamine.

The R.B.E. of Fission Neutrons, 250 kV X-rays, Cd(n, γ) and 60Co Gamma-rays for Intestinal and Haemopoietic Deaths in Guinea-pigs

SummaryA clearly defined intestinal syndrome was found in irradiated guinea-pigs. After irradiation with fission neutrons, X-rays, Cd(n, γ) or 60Co gamma-rays the LD50/6 was 755 rads, 1120 R, 1536 R and 1718 R respectively. The dose of radiation needed to produce haemopoietic damage was much less, and the corresponding LD50/30 values were 247 rads, 447 R, 493 R and 484 R, respectively. The LD50/30 was 7 per cent lower for dorso-ventral than ventrodorsal neutron-irradiation.R.b.e. values were slightly greater for intestinal than for haemopoietic deaths. The respective values were 2·3 and 2·0 for neutrons, 1·5 and 1·1 for 250 kV X-rays and 1·1 and 0·9 for Cd(n, γ) gamma-rays when compared with 60Co gamma-rays.