Long-term expression of transforming growth factor TGF beta1 in mouse skin after localized beta-irradiation

The long-term expression of TGF beta 1 in mouse skin after localized irradiation with a beta-emitting source is reported. The skin of CBA/ca mice was exposed to 50 Gy superficial beta radiation from an 11 mm strontium-90 source. Such a dose produced an acute moist desquamation reaction in 100% of the animals, which was macroscopically resolved within 30 days. The acute response was followed by progressive remodelling of dermal tissues as characterized by histological means. The expression of TGF beta 1 was followed for 12 months after irradiation and showed three distinct waves of expression at the RNA level. Levels of expression initially rose to 230% above controls at 6 h before returning to control levels around 24-48 h. Expression then rose again to 169 and 234% above controls at 14 and 28 days post-irradiation respectively. Levels then declined to those of the controls by 2 months. A progressive increase in expression was then noted after 3 months, which peaked around 9 months and was resolved by 12 months. In a parallel study the skin of 144 CBA/ca mice was exposed to 50 Gy superficial beta radiation from 2 x 4 cm Thulium-170 source and compared with a similar group of sham-irradiated controls. The irradiated group showed a cumulative tumour incidence of 54.3% compared with 0% incidence in the sham-irradiated group. Of the 45 radiation-induced tumours a representative sample of 16 (nine malignant fibrous histiocytomas; three fibrosarcomas; two fibromas; one squamous cell carcinoma; one rhabdomyosarcoma) were selected for further study. Semiquantitative PCR on all these tumours showed elevated levels of TGF beta 1 expression ranging from 1.8 to 87-fold above the levels found in normal skin. This study is part of ongoing investigations into the long-term effects of single accidental exposures. The 50 Gy dose used is comparable with the surface doses obtained by some of the victims of the Chernobyl accident.