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Increases in Sequence Specific DNA Binding by p53 following Treatment with Chemotherapeutic and DNA Damaging Agents¹

Stress Protein Group, Joint Center for Radiation Therapy, Boston, Massachusetts 02115

We have investigated the effect of chemotherapeutic and DNA damaging agents on binding of the tumor suppressor phosphoprotein p53 to its consensus DNA sequence. Activation of p53-DNA binding was seen for treatment with radiation, hydrogen peroxide, actinomycin D, Adriamycin, etoposide, camptothecin, 5-fluorouracil, mitomycin C, and cisplatin. These results showed that DNA strand breaks were sufficient to lead to increased levels of p53. The protein synthesis inhibitor cycloheximide blocks the increase in p53 following DNA damage. The increase in p53 activation in camptothecin treated cells may result, at least in part, from an increased half-life of the protein and consequent increases in intracellular protein concentration.

¹ Supported by NIH Grants R29CA-44940 and ROI 47407. R. B. T. was supported by an ASTRO Research Fellowship from the American Society for Therapeutic Radiology and Oncology.

² To whom requests for reprints should be addressed, at Joint Center for Radiation Therapy, 50 Binney Street, Boston, MA 02115.

Received 2/19/93. Accepted 4/ 1/93.

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