A p53 dose-response relationship for sensitivity to DNA damage in isogenicteratocarcinoma cells

Teratocarcinomas are tumors that arise from primordial germ cells and are r eadily curable with DNA-damaging chemotherapeutic drugs. Teratocarcinoma ce lls ex vivo in tissue culture are also relatively chemosensitive and underg o apoptotic death in response to DNA damage, We have previously hypothesize d that the observed sensitivity of this tumor type to DNA damage is related to high basal expression of wild-type p53 protein, We have now addressed t his issue by characterizing the DNA damage response of isogenic teratocarci noma cells that differ only in their level of expression of wild-type p53 p rotein, We find a clear p53 dose-response relationship in these cells for r apid apoptosis following DNA damage that correlates with diminished colony formation in clonogenic survival assays. These results suggest that strateg ies to increase basal wild-type p53 protein expression prior to treatment w ith DNA-damaging drugs may improve curability in other tumor types. Oncogen e (2001) 20, 2982-2986.