Expression of Transforming Growth Factor-β1 in Mouse Skin During the Acute Phase of Radiation Damage

Transforming growth factor-beta (TGF beta 1) plays a central role in wound healing, so its perturbation by radiation may contribute to the acute and late effects seen in irradiated skin. TGF beta 1 mRNA expression was measured by PCR, in the skin of the CD1 and CBA mouse, exposed to Sr-90 beta from an 11-mm diameter source. TGF beta 1 mRNA expression increased sharply after doses between 1 and 10 Gy and plateaued at approximately 200% above controls after doses between 20 and 50 Gy. Immunohistochemistry showed that the TGF beta 1 protein was confined to the dermis and suprabasal cells with none in basal cells. A dose of 50 Gy produces an acute desquamative reaction in 100% of mice that is resolved in 30 days. After the same dose, TGF beta 1 mRNA expression fell below the controls at 3 h (-9.4% in the CD1 and -44% in the CBA mouse); rose sharply at 6-12 h (+124% CD1, +230% CBA), returned to control levels by 24-48 h, then rose progressively to approximately 200% above the controls between days 7 and 14. TGF beta 1 mRNA expression remained elevated at 100-200% above controls until the end of the experiment at 55 days. The significance of these changes in TGF beta 1 is discussed in the context of the early stress response reaction to radiation, the acute inflammatory and the later chronic fibrosis of the skin.