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In Vivo Tests for a Carcinogenic Metabolite in Plasma of Animals Given Injections of Ethyl Carbamate (Urethan)

( Department of Experimental Biology, The Weizmann Institute of Science, Rehovcth, Israel)

Plasma, obtained from rabbits given injections of urethan hours previously, when administered intraperitoneally to Swiss mice, produced a significantly increased incidence of lung adenomas in these animals, as well as an increased incidence of skin papillomas at the site of subsequent croton oil applications.

These effects were not obtained when the plasma was lyophilized or desiccated, with the consequent removal of the free urethan. The condensed vapors collected during the process of lyophilization, on the other hand, were carcinogenic.

Carbonyl-labeled urethan-C¹⁴ was used to determine the urethan content of the plasmas and condensed vapors. The carcinogenic potencies for the lung and the initiating potencies for the skin were not significantly different from the effects of comparable amounts of free urethan.

The results obtained could, therefore, be entirely accounted for on the supposition that the carcinogenic effects were due to urethan itself, without the participation of a metabolite.

The possibility of the existence of such a metabolite is discussed in the light of the results obtained.

Received 6/15/59.