|Early and Delayed Radiation Effects After Localised Irradiation of Pigs and Rabbits
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|Purpose: To study the early radiation-induced necrosis and late radiation-induced fibrosis of skin and underlying tissues after acute localized irradiation with a view to the management of accidental over-exposure of man
Status: 1981 -
Treatment: 1) Single collimated gamma exposure (Ir-192) (diameter 2 cm) of the outer side of the thigh and the back of pigs with skin surface doses from 0 to 140 Gy;
2) Single collimated gamma exposure (Ir-192) (diameter 2 cm) of the outer side of the back of rabbits with skin surface doses from 0 to 160 Gy ;
3) Single beta exposure with a collimated (4cm diameter) Sr-90/Y90 source (1.7 GBq) of the flank of pigs;
4) Mixed exposure (11% Ir-192 gamma 91% Sr-90/Y90 beta) of the pig skin with doses from 3.2 Gy gamma + 32 Gy beta radiation to 8 Gy gamma + 80 Gy beta radiation
Dosimetry: LiF thermoluminescence dosimeter, ionization chamber
Endpoints: 1) Clinical, biochemical and biophysical evaluation of the diagnostic-prognostic evolution of the lesions in dependence of dose and time after exposure (serum biochemistry, microwave thermography, X-ray computerized tomography, NMR imaging and spectroscopy, vascular and metabolic scintigraphy, skin microrelief, cutaneous laser Doppler
2) Histological, histo-enzymological and immuno-cytochemical evolution in the irradiation skin and skeletal muscle;
3) Pharmacological trials and surgery early after acute local exposure;
4) Medical treatment of late radiation-induced fibrosis.
5) Molecular-biological studies: early and late response
Animal: Large white pigs (4 months old) and adult New Zealand rabbits
Results: The development of the lesions after dose levels such as encountered after accidental overexposure was studied in function of time, size of field and penetration of the radiation. The studies demonstrate the importance of an early assessment of the degree of damage for an effective therapy. The data show that a spectrum of tests rather than a single one is needed for such an evaluation. The methods most useful for such an early evaluation are microwave thermography and scintigraphic techniques. Enzymatic tests help to evaluated the inflammatory reaction and cutaneo-muscular necrosis. Early treatment with excision of irradiated skin only followed by early grafts is most effective after doses of 120-160 Gy to reduce the late extension of the fibronecrotic processes. Drugs which reduce aggregation of platelets and combat infection. Softening of the late fibrotic reaction could be achieved with superoxide dismutase.
Molecular-biological studies on the mechanism by which fibroblast proliferate and deposit extracellular matrix indicate that the fibrotic process after irradiation escapes normal control by the organism. It is thought that proto-oncogenes induced after irradiation, c-fos after as little as 0.5 Gy, result in an activation of the fibroblasts. An overproduction of transforming growth factors may play a role in the overproduction of collagen and the reduction in protein breakdown.
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