TRANSFECTION OF A VECTOR EXPRESSING WILD-TYPE P53 INTO CELLS OF 2 HUMAN GLIOMA CELL-LINES ENHANCES RADIATION TOXICITY

Replication-deficient adenovirus (Adv5)-based vectors containing eithe r wild-type p53 or the beta-gal marker gene were introduced into cells of the T98G (p53 mutant) and U87MG (p53 wild-type) human glioma cell lines. The wild-type p53 gene was successfully expressed in each cell line as shown by flow cytometry and Western blotting. The presence of the p53-expressing vector was toxic in both cell lines compared to con trol cells or to those containing the beta-gal vector. At levels of Ad v5p53 vector that produced detectable toxicity, the effect of irradiat ion was enhanced, producing a twofold increase in cell killing. In the T98G cells, the presence of the p53 vector resulted in an increase in the number of cells undergoing apoptosis after irradiation, whereas a smaller and only additive response was observed in the U87MG cells. C onversely, an increase in micronucleus formation, indicating corrupt m itotic activity, was observed in irradiated Adv5p53-positive U87MG cel ls but not in T98G cells. These data suggest that p53-expressing vecto rs effectively enhance radiation lethality in these human glioma cell lines, but that the mechanism of action cannot be simply related to ac tivation of the p53-dependent pathway to apoptosis. (C) 1998 by Radiat ion Research Society.