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Effects of Hydroxyurea on DNA and RNA Synthesis in Mouse Skin, Liver, and Thymus and on Skin Tumorigenesis Initiated by ß-Propiolactone¹

McArdle Laboratory for Cancer Research, University of Wisconsin Medical Center, Madison, Wisconsin 53706

Hydroxyurea was investigated as an inhibitor of DNA synthesis in the tissues of intact mice for extended periods of time. During administration of 5 mg of hydroxyurea i.p. every 45 min for 12 hr, incorporation of thymidine-³H into DNA of mouse skin, liver, and thymus was depressed to 5%, 25%, and 5%, respectively, of values found in saline-injected controls. Incorporation of cytidine-5-³H into RNA during drug administration was essentially unaffected by hydroxyurea. After the last of the multiple injections of the compound, DNA synthetic ability returned to normal levels in the skin and liver within 3–5 hours. Recovery of the ability to synthesize DNA was slower and more complicated in the thymus. Hydroxyurea showed little direct effect on RNA synthesis during the recovery period.

Multiple injections of hydroxyurea which blocked DNA synthesis for 12–15 hr had little or no effect on skin tumor incidence in mice initiated with ß-propiolactone before, during, or after administration of the drug.

¹ This work was supported in part by grants from the American Cancer Society (E-6) and the USPHS (TO1-CA-5002 and CA-07175).

² Present address: Division of Plastic Surgery, School of Medicine, University of North Carolina, Chapel Hill, N.C., 27515.

Received 3/11/68. Accepted 8/ 1/68.