THE INTERACTION OF TAXOL AND VINBLASTINE WITH RADIATION INDUCTION OF P53 AND P21(WAF1 CIP1)/

The combination of the microtubule active drug taxol with radiation ha s shown promise for use in combined modality therapy. Recent studies h ave demonstrated that radiation and a wide range of chemotherapy agent s, including microtubule active drugs, induce p53. In certain circumst ances, the induction of p53 has been shown to be an important paramete r in the response of a tumour to cytotoxic treatment. We examined the induction of p53 and its downstream target, p21(WAF1/CIP1), by the mic rotubule active agents taxol and vinblastine with radiation. An increa se in induction of both p53 and p21(WAF/CIP1) was demonstrated when ra diation was added to either taxol or vinblastine treatment. These resu lts, in conjunction with data on taxol and vinblastine induction of p2 1(WAF1/CIP1), suggest a rationale for the combination therapy.