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Comparison of Cytotoxicity of Hydroxyurea in Normal and Rapidly Proliferating Epidermis and Small Intestine in Mice¹

Institute of General and Experimental Pathology, University of Oslo, Rikshospitalet, Oslo 1, Norway

Cytotoxicity of hydroxyurea has been studied in mouse epidermis and small intestine by determining the loss of thymidine-³H-labeled DNA by both autoradiographic and biochemical methods. In the normal epidermis, hydroxyurea-induced cytotoxicity appears to be limited to some of the DNA-synthesizing cells, which are lost within 12 hr after hydroxyurea injection. Labeled cells that survive hydroxyurea treatment proceed through mitosis. A low dose of hydroxyurea, which inhibits DNA synthesis effectively for at least 1 hr, is not cytotoxic.

In rapidly proliferating epidermis 18 hr after an application of croton oil, the duration of the inhibition of DNA synthesis by a given dose of hydroxyurea is somewhat reduced, and the loss of prelabeled DNA is greatly reduced. In contrast, the extent of hydroxyurea-induced cytotoxicity in the rapidly regenerating small intestine 3 days after whole-body X-irradiation with 1000 R was only slightly less than that found under normal conditions. This difference between the number of cells killed by hydroxyurea in the two stimulated tissues may be related to the degree of increase in cell proliferation rate. The thymidine-³H labeling index in croton oil-treated epidermis was increased more than 10-fold, while that in the small intestine of X-irradiated mice was increased less than 2-fold.

¹ This work was supported in part by a grant from the American Cancer Society, Wisconsin Division.

² Present address: Bioassay Section, Experimental Pathology Branch, National Cancer Institute, NIH, Bethesda, Md. 20014.

Received 8/17/70. Accepted 11/ 4/70.