p53 induction and apoptosis in response to radio- and chemotherapy in vivois tumor-type-dependent

The p53 protein rapidly accumulates in cells in response to DNA damage, whi ch can trigger apoptosis. This pathway is hypothesized to be important for tumor suppression by p53, as well as for the response of tumors to chemo- o r radiotherapy. Implicit in these ideas is that the p53 induction-apoptosis pathway is active in tumor cells in vivo. Because tumor suppression by p53 in mice is markedly tissue-type-dependent, we tested the activity of the p athway in tumors in vivo by inducing tumors in six different tissues and tr eating tumor-bearing mice with DNA damaging cancer therapeutic agents. In r esponse to treatment, cells from T-cell lymphomas, intestinal adenomas, and mammary tumors rapidly induced p53 and underwent apoptosis. In squamous ce ll papillomas, p53 was constitutively expressed and was further induced by the treatments, but apoptotic cells were only rarely observed. In treated m ice bearing lung or liver adenomas, minimal or no p53 accumulation or apopt osis was observed in the tumor cells. Thus, there is marked variation in th e intrinsic ability of autochthonous tumor cells to accumulate p53 and unde rgo apoptosis. This variation provides one explanation for the tissue speci ficity of tumor suppression by p53. It also indicates that the role of apop tosis in the response of tumors to therapy varies significantly among tumor types.