EARLY AND LATE EFFECTS OF RADIATION ON THE SKIN

Ziel

A broadly based programme of clinical and experimental research is proposed. This will address many of the problems related to the improvement of radiation protection criteria for the skin, and the search for improved treatment modalities for the skin and subcutaneous tissues following local, accidental overexposure.
The pathogenesis of early and late radiation induced changes to the skin have been evaluated extensively in the pig, since the skin of this species is both grossly and histologically similar to that of man. Early effects have been examined after irradiation with X-rays and beta rays from sources emitting a range of beta energies. The effects of changing source size has also been evaluated. Late radiation effects, represented largely by tissue atrophy, have been examined for periods up to 2 years after irradiation.

The results have indicated that the type of radiation responses observed depend both on the area of skin exposed and on the energy of the radiation. Exposures resulting from contact with discreet radioactive particles (hot particles) or radioactive source of low energy, which are poorly penetrated into tissue, produce effects that are different mechanistically from those seen after more generalised exposure. This has not been recognised until recently and the usage of the same terminology to describe both sets of lesions has, in the past, caused considerable confusion.

These investigations provide, for the first time, a detailed understanding of the types of reactions that may be encountered in the skin after exposures that are of relevance to radiation protection. This is of considerable benefit to the European Communities Radiation Protection Programme, providing a better scientific basis for future investigations related to radiological protection and skin exposure.

Studies have been carried out on the skin of pigs to determine the dose related changes in the acute response from 3 beta emitters, strontium-90 (high energy), thulium-170 (intermediate energy) and promethium-147 (low energy). Irradiation has been with sources which varied in size from 0.1 to 40 mm in diameter. Exposures from these sources were considered to be acute exposures, in that they had a maximum duration of less than or equal to 2 hours. For a 22.5 mm diameter source of strontium-90 the effects of radiation dose rate have been examined.

The effects of the area of tissue irradiated on the severity of late dermal atrophy has also studied at 2 years after irradiation from strontium-90 and thulium-170 sources.

In an extensive series of studies, dose effect relationships have been established for the endpoints of early moist desquamation and late dermal atrophy after the irradiation of areas of skin of greater than or equal to 19.5 square millimetres and for acute ulceration and late dermal atrophy after hot particle exposure. A hot particle refers to a source of less than equal to 2 mm diameter. For irradiations involving the very low energy beta emitter, promethium-147, the dose related incidence of acute epidermal necrosis was investigated for sources of differing size. The data provide, for the first time, a rational guide for the development of improved radiological protection criteria for the skin. The information has provided a major contribution to both International Commission on Radiological Protection (ICRP) and NRCP task group reports relating to the problems of skin exposure.

Studies have been carried out into the effects of variations in dose rate, from sources of strontium-90, yttrium-90, on the acute radiation response of the skin of the pig. Irradiation was with a standard 22.5 mm diameter plaque and the dose rates that have been used to date have ranges from 2.2 cGy/min to 10.7 cGy/min. The results from these exposures have been compared with those produced by a high dose rate source of 300 cGy/min. For the low dose rate studies, strontium-90, yttrium-90 plaques were mounted in nylon holders which could be sutured to the skin for the period of irradiation, which ranged from a few hours to approximately 3.5 days. Pigs were only anaesthetized for the times of application and removal of the plaques.
After irradiation the sites of irradiation were assessed at weekly intervals for 9 weeks, by at least 3 independent observers, for the presence or absence of moist desquamation and the severity of erythema. For each of the low dose rates investigated there was a clearly defined dose effect relationship, however, the dose effect curves were progressively shifted to the right as the dose rate was reduced. At the dose levels associated with the 50% incidence of moist desqumation (ED50) the dose modification factors, when compared with the high dose rate 300 cGy/min source, were 1.5 1.7 and 2.4 for sources with dose rates of 10.7 5.2 and 2.2 cGy/min, respectively. At the dose giving 10% incidence (ED10) and estimated threshold dose for moist desquamation, the dose rate effect was, on the basis of the experimental data, less clearly defined. However, the fitted dose effect curves still suggested modification factors of a similar order of magnitude.

Late changes in the skin of pigs, assessed by a measurement of the relative changes in dermal thickness, have been evaluated after irradiation from a 20 by 40 mm thulium-170 plaque. Exposure was to single doses of 30, 40, 80 and 120 Gy at the skin surface at a dose rate of 1 Gy/min. Doses of 30 , 40 and 80 Gy have previously been shown to be associated with a 15%, 25% and 35% reduction in relative dermal thickness, respectively, based on measurements of dermal thickness in histological sections 104 weeks after irradiation from a 19 mm diameter source. No previous studies had been carried out as to the likely severity of damage after a dose of 120 Gy.
Serial assessments of the severity of any late dermal changes were obtained at intervals of 12, 14, 16, 18, 20, 22, 26, 44 and 52 weeks after irradiation, using a noninvasive A scan ultrasound technique. These time intervals were selected as previous studies after strontium-90, yttrium-90 irradiation had indicated 2 distinct phases of reduction in relative dermal thickness; the initial phase between weeks 12 and 22 and a later phase at approximately 52 weeks.
Observations carried out for up to 52 weeks after thulium-170 irradiation have shown a pattern of changes qualitatively similar to those seen after strontium-90, yttrium-90 exposure. There was an initial reduction in relative dermal thickness between 12 and 22 weeks after irradiation, the severity of which was dose dependent (the reduction ranging from between 10% and 15%). There was then evidence for a second phase of reduction in relative dermal thickness at approximately 52 weeks after irradiation but additional measurements, at later times after irradiation, will be required before the magnitude of the effect can be fully evaluated. It is proposed to continue to assess changes for periods up to 104 weeks after irradiation.
The increased use of radioisotopes in medicine and in scientific research and problems inherent in the safe operation of nuclear power plants has increased concern about the present ICRP guidelines for the skin. This concern stems from the paucity of biological data on which the present guidelines are based and the potential overrestrictive nature of present criteria, as for example in the nuclear industry with respect to unique exposures to small radioactive particulates. These factors have important economic and technical consequences for the CEC. Although the results of recent experiments have provided valuable information, some important questions still need to be answered. It is proposed to carry out studies to determine the anatomical site of the target cells responsible for the different types of effect observed; this will indicate the depth in skin at which relevant dose measurements should be made. Although the results obtained from pig skin will provide the most relevant data for nonstochastic ris s, a comparison of the results obtained with those for mice will help in the identification of target cells. Studies in mice will help in the understanding of the stochastic risk. Both species will be used to evaluate the effects of irradiation with very low energy beta rays, alpha-particles, and small radioactive particulates with emissions of varying energy.

The possible synergistic effects of acute skin damage as a codeterminant of survival, when combined with total body irradiation, will be investigated in mice, and the effect of radiation on wound healing will be studied in pigs.

The contribution of the CRC Normal Tissue Radiobiology Research Group can be described under two broad headings:
research related towards the improvement of radiological protection criteria;
a better understanding of the pathophysiology of late radiation damage to the skin leading to potential improvements in treatment.

Radiological protection criteria

The early and late nonstochastic effects of radiation will be studied in an experimental model system, namely the pig, whose skin structure and anatomical dimensions closely match those of man. Dose-effect relationships will be evaluated after exposure of the skin to different radiation energies with the specific intention of establishing threshold doses for different effects. There will be an evaluation of the anatomical site(s) and the target cell population(s), damage to which results in the various effects observed.

Pathogenesis of late radiation-induced damage, a guide to improved treatment modalities.

Following the accidental overexposure of the skin to radiation a late wave of erythema may develop after the main erythema reaction has faded. This late phase of injury represents vascular insufficiency in the dermal and subcutaneous tissues and is associated with oedema. This may in itself contribute further to any primary vascular changes. Severe vascular impairment will result in the development of necrosis to the dermis and deeper tissues when overexposure is to high energy radiations. It is proposed to study further these adverse reactions in pig skin by examining radiation-induced changes in vascular permeability. Radiation dose-related and energy-related changes in lymphatic clearance will be evaluated using a recently developed, 99mTc-Rhenium sulphide colloid, clearance technique.

Wissenschaftliches Gebiet

Programm/Programme

FP1-RADPROT 6C - Multiannual research and training programme (Euratom) in the field of radiation protection, 1985-1989

Thema/Themen

Data not available

Aufforderung zur Vorschlagseinreichung

Data not available

Finanzierungsplan

CSC - Cost-sharing contracts

Koordinator

University of Oxford

EU-Beitrag

Keine Daten

Adresse

Old Road Headington
OX3 7LJ Oxford
Vereinigtes Königreich

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