Transforming Growth Factor- 1 Mediates Cellular Response to DNA Damage in Situ

Transforming growth factor (TGF)1 is rapidly activated after ionizing radiation, but its specific role in cellular responses to DNA damage is not known. Here we use Tgf 1 knockout mice to show that radiationinduced apoptotic response is TGF1 dependent in the mammary epithelium, and that both apoptosis and inhibition of proliferation in response to DNA damage decrease as a function of TGF1 gene dose in embryonic epithelial tissues. Because apoptosis in these tissues has been shown previously to be p53 dependent, we then examined p53 protein activation. TGF1 depletion, by either gene knockout or by using TGFneutralizing antibodies, resulted in decreased p53 Ser-18 phosphorylation in irradiated mammary gland. These data indicate that TGF1 is essential for rapid p53-mediated cellular responses that mediate cell fate decisions in situ.