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Multipotential Carcinogenicity of Urethan in the Sprague-Dawley Rat^*

Albert Tannenbaum, S. D. Vesselinovitch, Cesare Maltoni and D. Stryzak Mitchell

( Department of Cancer Research, Medical Research Institute, Michael Reese Hospital and Medical Center, Chicago, Illinois)

These investigations are concerned with the neoplastic response to urethan (ethyl carbamate) of inbred Sprague-Dawley rats permitted to live out their life span. The carcinogen was administered to male and female animals either intraperitoneally or in drinking water.

Urethan significantly potentiated the formation of benign mammary tumors and carcinomas of the sebaceous gland (Zymbal) of the external auditory canal; it apparently enhanced the development of angiomas and sarcomas at various sites; and it induced malignant lymphomas, tumors of the kidney, and neurofibrosarcomas of the ear. In addition, other tumor types were observed in appreciable numbers, but their significance is equivocated by comparison with similar tumors arising in controls that had a longer average life span.

Untreated controls, inbred Sprague-Dawley rats, developed many types of neoplasms, and the findings augment and extend the information in the literature on the incidence and average age at appearance of these spontaneous tumors. Three of 105 untreated control animals developed carcinomas of the sebaceous gland (Zymbal) of the external auditory canal at an average age of 115 weeks. As far as we know, this tumor has never been previously reported as occurring spontaneously.

The multipotential carcinogenicity of urethan in a number of species and the similarity of response of a particular tissue to various carcinogenic agents are discussed.

^* This work was supported by Research Grant C-3787 from the National Institutes of Health, U.S. Public Health Service.

Research Associate during 1959 and 1960. Present address: Istituto di Patologia Generale, Università di Bologna, Italy.

Supported, in part, by the Foundation for Cancer Research, Chicago.

Received 7/27/62.