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Macromolecular Synthesis following a Single Application of Polycyclic Hydrocarbons Used as Initiators of Mouse Skin Tumorigenesis¹

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

After the application of initiating doses of polycyclic aromatic hydrocarbons, the incorporation of thymidine-³H, cytidine-³H, and leucine-³H into DNA, RNA, and protein, respectively, in mouse skin epidermis was determined. Parallel histological changes were correlated. A single initiating dose (0.05 or 0.10 µmole) of 7,12-dimethylbenz[a]anthracene depressed DNA synthesis for 24 hr without a subsequent increase; there was no detectable epidermal hyperplasia, nor was RNA or protein synthesis altered. In contrast, 7,12-dimethylbenz[a]anthracene applied in sufficient quantity to result in tumor formation after a single dose (0.6 or 1.2 µmoles) caused a larger and more protracted inhibition of DNA synthesis, followed by a gradual increase above control level. Inflammation was evident at 6 days and, by 10 days after treatment, some visible wounding was observed and RNA and protein synthesis were stimulated. Initiating doses of 1,2,5,6-dibenz[a]anthracene gave results similar to initiating doses of DMBA; there was an early inhibition in DNA synthesis that was not followed by a stimulation. 1,2,3,4-Dibenzanthracene, a weak or inactive initiating agent, produced a large peak of RNA synthesis at Day 1, but DNA synthesis was close to control values at all times studied and, histologically, the skin sections appeared normal. 7,12-Dimethylbenz[a]anthracene, applied to skin in which DNA synthesis was stimulated 3-fold by acetic acid, blocked the increased incorporation of thymidine-³H into DNA.

¹ This work was supported in part by Grant BC-14 from the American Cancer Society and Grants CA-07175 and CA-05002 from the National Cancer Institute.

² Present address: Pacific Northwest Research Foundation (Fred Hutchinson Cancer Research Center), 1102 Columbia Street, Seattle, Wash. 98104.

Received 6/25/73. Accepted 12/21/73.

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