We have examined the relationship to tumor formation of the stimulated phospholipid metabolism produced in mouse skin by a single application of the tumor-promoting phorbol ester, 12-O-tetradecanoyl-phorbol-13-acetate (TPA). The TPA-induced stimulation of 32P incorporation into mouse skin phospholipids was first characterized and then compared with the altered incorporation of 32P produced by the application of either acetic acid, β-propiolactone or 7, 12-dimethylbenz[a]anthracene at 2 dose levels. The results indicated that only the tumor promoter, TPA, was able to stimulate the early synthesis of phosphatidylethanolamine and phosphatidylcholine. This specificity was further emphasized by the demonstration that only TPA stimulated the incorporation of choline-14C into phosphatidylcholine and ethanolamine-3H into phosphatidylethanolamine. The finding that mouse skin papillomas (initiated with 7,12-dimethylbenz[a]anthracene and promoted with croton oil) contained more phosphatidylcholine than the tissue of origin suggested that membrane alterations and the stimulated synthesis of phosphatidylcholine are important factors in tumor formation.

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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.

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