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Arginase Activity and Nitrogen Content in Epidermal Carcinogenesis in Mice^*

(From the Department of Anatomy, Washington University School of Medicine, St. Louis, Missouri)

1. Determinations were made of arginase activity, total nitrogen, trichloroacetic acid soluble nitrogen, urea, and preformed ammonia in mouse epidermis treated with pure benzene or benzene containing croton oil or methylcholanthrene, and in transplantable squamous cell carcinomata originally derived from the skin of mice painted with methylcholanthrene solution.

2. All of the tissues studied showed a marked increase in arginase activity upon heating at 50°C. for 5 hours in 0.05 M MnCl₂.

3. The arginase activity, total nitrogen, and the wet weight of the epidermis per mouse all increased to a maximum after 3 paintings with benzene containing methylcholanthrene and decreased after subsequent applications of the carcinogen. The maximal mean value for arginase activity was 3 times that found in the untreated epidermis. The percentage of the total nitrogen found in the TCA-soluble fraction was lowest after 3 paintings.

4. In Tumors I and II the mean arginase activities were approximately 6 and 18 times, respectively, that of the normal epidermis on a wet weight basis and 11 and 33 times on a total nitrogen basis. The percentage of the total nitrogen found in the TCA-soluble fraction of the tumor samples studied was lower than in any of the samples of epidermis.

5. Six and 11 paintings of benzene alone produced a two fold increase in arginase activity, a decrease in total nitrogen content, and an increase in TCA-soluble nitrogen.

6. Three applications of methylcholanthrene in benzene caused a decrease in epidermal urea in adult mice to approximately 55 per cent of the normal value. No further decrease took place in tissues receiving 6 and 24 paintings of the carcinogen. No significant changes from normal were noted in the ammonia content of these tissues.

7. The level of urea decreased further in tumors to a value approximately one-third of that found in normal epidermis and the ammonia decreased to approximately the same extent.

8. The results were discussed with special reference to previous studies made on similarly prepared material.

^* Aided by grants from the U.S. Public Health Service and the Charles F. Kettering Foundation.