SEPARATE PATHWAYS FOR P53 INDUCTION BY IONIZING-RADIATION AND N-(PHOSPHONOACETYL)-L-ASPARTATE

The tumor suppressor gene product, p53, appears to be a significant pa rticipant in signaling pathways that mediate cellular responses to cyt otoxic stresses. In particular, p53 appears to be a critical determina nt of whether the cell lives or dies and how it progresses through the cell cycle after the cytotoxic exposure, Many of the molecular detail s for these signaling pathways remain to be elucidated, and whether al l cytotoxic signals utilize the same pathway to increase p53 expressio n is not clear, Here, we demonstrate the existence of cell types in wh ich the induction of p53 and associated G(1) arrest by the antimetabol ite, N-(phosphonoacetyl)-L-aspartate (PALA), is defective, whereas p53 induction and G(1) arrest induced by ionizing radiation are intact, T hese observations demonstrate the existence of genetic defects that ca n alter p53 induction and associated cellular outcomes after some, but not all, cytotoxic insults and suggest distinct pathways of p53 induc tion by PALA and ionizing radiation.