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.

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.

Reflections on the terms stochastic and non-stochastic as currently used in radiological protection.

The meanings, past and present, of the word stochastic are discussed and related to the way in which "stochastic" and "non-stochastic" may be used to describe the categories of biological damage from ionizing radiation. "Haplocytic" and "polycytic" are suggested as alternatives: these terms allow a classification according to the numbers of cells involved initially and, therefore, according to the basic mechanisms. For more speculative concepts relating to carcinogenesis the word "syncytic" is suggested, together with some potentially useful terms derived from it.

Tumour incidence and longevity in neutron and gammairradiated rabbits, with an assessment of r.b.e.

Rabbits were kept for the whole of their natural life-span (6--9 years) after exposures of 440--1410 rad of gamma-rays or 180--550 rad fission neutrons. Irradiated rabbits did not live as long as unirradiated controls but the difference was statistically significant only after the higher doses of neutrons. Earlier deaths were explained by increased incidences of a wide variety of tumours. The increases were statistically significant for basal-cell tumours of the skin, fibroasarcomas, osteosarcomas and Sertoli-cell tumours of the testis. Other phenomena assoicated with natural ageing were unchanged or decreased in irradiated rabbits. The r.b.e. of the neutrons was assessed as 3--3.5 for tumour induction and 3x5--4x0 for longevity. Comparisons with previous data on acute and subacute effects suggest that the r.b.e. increased linearly with the logarithm of time for 5--2000 days after irradiation.

An inbred strain of rats with a high incidence of squamous-cell carcinomas of the mouth.

Intra-oral squamous-cell carcinomas occurred in over 50% of the HMT inbred strain of rats. In the outbred stock from which it was derived the incidence was 5% or less, both when inbreeding was begun and after the inbred strain was fully established. Various factors in food and husbandry which might have irritated the oral mucosa were investigated, but there was no signficiant evidence that they played any part in the high incidence of mouth tumours. It is concluded that there must have been an accidental selection during inbreeding in favour of rats which had an inherited tendency to develop squamous-cell carcinoma of the mouth. There are a number of similarities between the rat tumour and intra-oral squamous-cell carcinoma in man and it is suggested that the rat tumour could be used as a model of the human disease.

A model for treating post-irradiation nausea and vomiting in man: the action of insulin in abolishing radiation-induced delay in gastric emptying in the rat.

Radiation-induced delay in gastric emptying in rats, which may be comparable to radiation-induced nausea and vomiting in man, can be successfully treated with insulin. Biphasic insulin, given in the appropriate dose for the radiation exposure, restored the rate of emptying to normal and was used instead of soluble insulin which made the stomach empty quicker than normal. Some of the evidence suggests that this effect of insulin is related to its action on carbohydrate metabolism, but there was no simple correlation between the hypoglycaemic action of insulin and its effect on stomach emptying. A complete explanation for this action of insulin cannot be given at this stage but the possible involvement of intestinal hormones, such as enteroglucagon is discussed. It is suggested that the use of insulin to treat radiation-induced nausea and vomiting in man should be considered.