Mutation of the p53 gene in human astrocytic tumours correlates with increased resistance to DNA-damaging agents but not to anti-microtubule anti-cancer agents.

ABSTRACT

Astrocytic tumours often become resistant to a variety of chemotherapeutic agents in advanced stages and frequently possess mutations in the p53 tumour-suppressor gene. Previous studies using established cell lines to investigate the relation between mutated p53 genes and altered resistance to anti-cancer agents brought inconsistent results. In this report, we examined the status of the p53 gene in 56 astrocytic tumour specimens by single-strand conformation polymorphism and their in vitro chemosensitivity to 30 different kinds of anti-cancer agents. The chemosensitivity was determined by drug-induced cell death using flow cytometry. We found that the mutated p53 gene correlated with increased resistance to DNA-damaging agents but the sensitivity to anti-microtubule agents was independent of the mutation, suggesting a clinical significance of the status of p53 gene in astrocytic tumours and a rational application of anti-microtubule agents to the patients with p53-mutated astrocytic tumours.