MUTATION OF THE P53 GENE IN HUMAN ASTROCYTIC TUMORS CORRELATES WITH INCREASED RESISTANCE TO DNA-DAMAGING AGENTS BUT NOT TO ANTI-MICROTUBULEANTICANCER AGENTS

Astrocytic tumours often become resistant to a variety sf chemotherape utic agents in advanced stages and frequently possess mutations in the p53 tumour-suppressor gene. Previous studies using established cell l ines to investigate the relation between mutated p53 genes and altered resistance to anti-cancer agents brought inconsistent results. In thi s report, we examined the status of the p53 gene in 56 astrocytic tumo ur specimens by single-strand conformation polymorphism and their in v itro chemosensitivity to 30 different kinds of anticancer agents. The chemosensitivity was determined by drug-induced cell death using flow cytometry. We found that the mutated p53 gene correlated with increase d resistance to DNA-damaging agents but the sensitivity to anti-microt ubule agents was independent of the mutation, suggesting a clinical si gnificance of the status of p53 gene in astrocytic tumours and a ratio nal application of anti-microtubule agents to the patients with p53-mu tated astrocytic tumours.