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The Binding of ß-Propiolactone to Mouse Skin DNA in Vivo; Its Correlation with Tumor-initiating Activity¹

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

ß-Propiolactone, an initiator of mouse skin tumors, was tested for binding to mouse skin DNA in vivo. ß-Propiolactone-³H in acetone was applied to the skin and 4 hr later DNA-bound tritium was determined. Binding was found to be a linear function of dose up to 480 µmoles of ß-propiolactone/mouse, with a marked decrease in the slope of the binding curve above 480 µmoles. After a single application of ß-propiolactone followed by repeated applications of croton oil, the tumor incidence showed a similar relationship to dose, indicating proportionality of tumor incidence to dose up to the 480-µmole level and a marked slope decrease above 480 µmoles. Further correlations of the degree of ß-propiolactone binding with tumor incidence were found when mice sensitive and mice resistant to ß-propiolactone were tested. DNA from ß-propiolactone-³H-treated mouse skin was hydrolyzed and chromatographed on paper. A strip scan of the chromatogram showed a single radioactive peak. The ³H-containing material was eluted and shown by UV spectral and R_F data to be 7-(2-carboxyethyl)guanine. Two weeks after ß-propiolactone-³H application, the radioactivity bound to skin DNA was reduced to less than 6% of the 2-hr level. The data are discussed in relation to the possible mechanisms of ß-propiolactone tumor-initiating activity.

¹ This work was supported in part by grants from the American Cancer Society (E-6), the Alexander and Margaret Stewart Trust Fund, and the USPHS (CRTY-5002).

Received 10/11/65. Revised 2/ 2/66.