Replication-deficient adenovirus (Adv5)-based vectors containing either wild-type p53 or the β-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 control cells or to those containing the β-gal vector. At levels of Adv5p53 vector that produced detectable toxicity, the effect of irradiation 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. Conversely, an increase in micronucleus formation, indicating corrupt mitotic activity, was observed in irradiated Adv5p53-positive U87MG cells but not in T98G cells. These data suggest that p53-expressing vectors effectively enhance radiation lethality in these human glioma cell lines, but that the mechanism of action cannot be simply related to activation of the p53-dependent pathway to apoptosis.

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