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I. Effect on DNA Synthesis in Vivo

William H. Eaglstein, MD; Gerald D. Weinstein, MD; Phillip Frost, MD

Arch Dermatol. 1970;101(2):132-139.

Abstract
Normal skin and actinic keratoses were exposed to fluorouracil in order to study its effect on deoxyribonucleic acid (DNA) synthesis. Using intradermally injected tritiated deoxyuridine and autoradiography, we have demonstrated that fluorouracil blocks DNA synthesis in vivo by inhibiting thymidylate synthetase activity. Fluorouracil administered intradermally blocks DNA synthesis in both normal skin and actinic keratoses. Applied topically, and topically with occlusion, fluorouracil inhibits DNA synthesis for two and four hours respectively in actinic keratoses. An estimated minimum tissue concentration of 10-⁴ to 10-⁵ M of fluorouracil was required to inhibit thymidylate synthetase activity in human skin. Possible correlation of this biochemical effect with the clinical action of fluorouracil on actinic keratoses is discussed.

Author Affiliations
Miami, Fla

From the Department of Dermatology, University of Miami School of Medicine, Miami, Fla.

Footnotes
Accepted for publication Sept 9, 1969.

Reprint requests to Department of Dermatology, University of Miami School of Medicine, PO Box 875, Biscayne Annex, Miami, Fla 33152 (Dr. Weinstein).

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