Lung tumour induction in mice after uniform and non-uniform external thoracic X-irradiation.

The aim of this study was to investigate the validity of the ICRP procedure of using average tissue/organ dose in estimating carcinogenic risk. It has been suggested that highly non-uniform exposure ('hot spots') is much more carcinogenic than an equivalent dose delivered uniformly. In a series of experiments, mice were irradiated with X-rays either uniformly to the thorax or non-uniformly with 72 1-mm microbeams which irradiated approximately 20 per cent of the total lung volume. Two experiments involving uniform irradiation showed a peaked tumour incidence curve with a maximum at 5 Gy. The first 'microbeam' study also produced a pronounced peak in the dose response with a maximum tumour incidence at 1 Gy average lung dose or 5 Gy to the irradiated lung tissue. This implied the use of average tissue dose might underestimate the carcinogenic hazard of non-uniform exposure. Later, more extensive, microbeam experiments failed to replicate this finding. The results were nearly similar to those for uniform irradiation, with a slight increase in tumour incidence from 2.5-5.0 Gy average lung dose. These results imply that for these irradiation conditions the ICRP dose averaging procedure remains valid.

Late nonstochastic changes in pig skin after beta irradiation.

Late radiation-induced changes in pig skin have been assessed following irradiation with beta-rays from a 22.5- or 15-mm-diameter 90Sr/90Y source and a 19- or 9-mm-diameter 170Tm source. Late damage, in terms of dermal atrophy, was assessed 2 years after irradiation from measurements of dermal thickness in irradiated and normal skin. After 90Sr irradiation maximum atrophy, a dermal thickness of 40-50% of the control value, occurred at a dose of approximately 40 Gy from the 22.5-mm source and approximately 75 Gy from the 15-mm source. In the case of 170Tm the 19- and 9-mm sources produced similar degrees of atrophy at equal doses. Maximum atrophy occurred at approximately 70 Gy, when the dermis was approximately 70% of the thickness of normal skin. Significant late tissue atrophy was seen at doses, from both types of radiation, which only produced minimal erythema in the early reaction. Such late reactions need to be taken into account when revised radiological protection criteria are proposed for skin.

Repopulation in irradiated pig skin: late versus early effects.

In the first 16 weeks after irradiation, two distinct waves of reaction can be observed in pig skin, the first wave (3-9 weeks) represents the expression of damage to the epithelium while the second is indicative of primary damage to the dermis, mediated through vascular injury. Following beta-irradiation with a strontium-90 applicator, a severe epithelial reaction was seen with little subsequent dermal effects. X-rays (250 kV), on the other hand, produced a minimal epithelial response at doses which led to the development of dermal necrosis after 10-16 weeks. Comparison of single doses with two equal doses separated by 28 days produced a D2-D1 value of 14.0 Gy at the doses which produced moist desquamation in 50% of fields (ED50) after strontium-90 irradiation. After X-irradiation, comparison of ED50 doses for the later dermal reaction suggested a D2-D1 value of 4.2 Gy. These values of D2-D1 for epithelial and dermal reactions in pig skin were compared with earlier data from this laboratory for similar split-dose experiments with a one-day interval. Such a comparison allowed for the estimation of the component of recovery in the present 28-day interval experiments due to repopulation. This component was found to be 6.5 Gy for the early epithelial damage, but was zero for the later dermal damage.

Split-dose recovery in epithelial and vascular-connective tissue of pig skin.

In the first 16 weeks after irradiation, two distinct waves of reaction can be observed in pig skin; the first wave (3-9 weeks) represents the expression of damage to the epithelium while the second is indicative of primary damage to the dermis, mediated through vascular injury. Following beta-irradiation with a strontium-90 applicator, a severe epithelial reaction was seen with little subsequent dermal effects. X-rays (250 kV) on the other hand, produced a minimal epithelial response at doses which led to the development of dermal necrosis after 10-16 weeks. Comparison of single doses with two equal doses separated by 24 h produced a D2-D1 value of 7.0 Gy at the doses which produced moist desquamation in 50% of fields (ED50) after strontium-90 irradiation. After X-irradiation comparison of ED50 doses for the later dermal reaction suggested a D2-D1 value of 4.5 Gy. Over this same dose range of X-rays the D2-D1 value for the first wave epithelial reaction was 3.5 Gy. These values of D2-D1 for epithelial and dermal reactions in pig skin were compared with published data and were examined in relation to the theoretical predictions of a linear quadratic model for tissue target cell survival. The results were broadly in keeping with the predictions of such a model.

Nonstochastic effects of different energy beta emitters on pig skin.

Circular areas of pig skin from 1- to 40-mm diameter were irradiated with beta emitters of high, medium, and low energies, 90Sr, 170Tm, and 147Pm, respectively. The study provides information for radiological protection problems of localized skin exposures. During the first 16 weeks after irradiation 90Sr produced a first reaction due to epithelial cell death followed by a second reaction attributable to damage to the dermal blood vessels. 170Tm and 147Pm produced the epithelial reaction only. The epithelial dose response varied as a function of beta energy. The doses required to produce moist desquamation in 50% of 15- to 22.5-mm fields (ED50) were 30-45 Gy from 90Sr, approximately 80 Gy from 170Tm, and approximately 500 Gy from 147Pm. A model involving different methods of epithelial repopulation is proposed to explain this finding. An area effect was observed in the epithelial response to 90Sr irradiation. The ED50 for moist desquamation ranged from approximately 25 Gy for a 40-mm source to approximately 450 Gy for a 1-mm source. The 5-, 9-, and 19-mm 170Tm sources all produced an ED50 of approximately 80 Gy, while the value for the 2-mm source was approximately 250 Gy. It is also suggested that the area effects could be explained by different modes of epithelial repopulation after irradiation. After high energy beta irradiation repopulation would be mainly from the field periphery, while after lower energy irradiation repopulation from hair follicle epithelium would predominate.

Implications of tissue target-cell survival-curve shape for values of split-dose recovery doses: late versus early effects.

Recent data from this laboratory on split-dose recovery for early and late effects in pig skin are consistent with the linear-quadratic model for cell survival, and with relative cell survival-curve shapes for early- and late-effect target cells where the early-effect cells have an initially steeper and straighter survival-curve than the late-effect cells.

The effects of negative pions on spermatogonial survival in the mouse.

A study of the radiation effects of pi-mesons on the testes of the mouse has been carried out using the pion beam at the SRC Rutherford Laboratory. The cell killing effects on type B and intermediate spermatogonia have been assessed and compared with the effects of 20-0 kVp X rays, delivered at the same dose rate. It was found that not only did irradiation of the testes not disturb the kinetics of spermatogenesis, but also the RBE for pions measured in the Bragg peak and on the plateau was not significantly different from unity. The comparison of this result with those of others using other pion beams is discussed.