Urethan (ethyl carbamate) as a multipotential carcinogen in BALB/C, ZB and DB female mice.

1. The objective of this investigation was to test the influence of mammary cancer tissue extract on the induction of various tumors by urethan. Three strains of female mice, Balb/c, Zb and Db, were used in this experiment. 2. It was found that urethan was a multipotential carcinogen in the induction of (a) lung tumor, ovarian hemorrhagic cyst, and hemorrhagic lesions in various tissue in Balb/c mice, (b) lung tumor, hepatoma, leukemia, mammary cancer, Harderian gland tumor and hemorrhagic lesions in various tissues such as spleen, mesenteric lymphnode, liver and ovary in Zb strain, and (c) lung tumor, mediastinal lymphoma, leukemia, hepatoma and hemorrhagic lesions in the liver and ovary in Db mice. 3. Mammary cancer tissue extract seemed to have a promotive effect on the generalization of the mediastinal lymphoma induced by urethan in Db female mice. ∗Copyright c ©OKAYAMA UNIVERSITY MEDICAL SCHOOL Acta Med. Okayama 16, 253-264 (1962) URETHAN (ETHYL CARBAMATE) ASA MULTIPOTENTIAL CARCINOGEN IN BALB/C, ZB AND DB FEMALE MICE Noriaki IDA, Nobuo ODA, Tadao YODA and Takashi KIYAMA* M. D. Anderson Hospital and Tumor Institute, The University of Texas, Department of Pediatrics (Chief: Dr. Grant H. Taylor) ( Research Fellows of M. D. Anderson HosPital) and Tumor Institute, The Univarsity of Texas. Received for publication, September 17, 1962 The objective of this investigation was to test the influence of mammary cancer tissue extract on the induction of various tumors with urethan. NETTLESHIP, HENSHAW and MEYER reported that ethyl carbamate (urethan) induced multiple pulmonary tumors in C3H mice exposed to roentgen rays. Since then, it has been generally accepted that urethan was one of the carinogens that produce lung adenomas in mice2-6. It was also demonstrated in our laboratory that urethan augmented in mice the induction of leukemia by X-rays, estrogenic hormone, or methy1cholanthrene• More recently, it was pointed out by TANNENBAUM and SILVERSTONE that urethan was a multipotential carcinogen, capable of inducing or augmenting pulmonary adenomas, mammary carcinoma, malignant mesenchymal tumors in the interscapular fat, cystadenomas of the lacrimal gland, and blood cysts in the liver in mice. In addition, HESTON, VLAHAKIS and DERINGER reported that repeated injections of urethan induce hepatomas which were larger in size than those in the uninjected controls, although the numbers of the tumors were not shown to be greater than those in the mice Teceiving a single injection. LIEBELT also observed a high incidence of hepatoma in Zb mice, (higher in male than female) after a single injection of urethan at birth. Interesting findings of the studies here described include (1) development of lung tumor, mediastinal lymphoma, systemic generalized stem cellleukemia, hepatoma, hemorrhagic lesions in the liver, and enlarged hemorrhagic mesenteric lymphnode, and enlarged ovaries (polyfollicular ovaries) in an individual female mouse of Zb strain, (2) the association of lung tumor, huge ovarian hemorrhagic cyst in an individual Balb/c mouse and (3) the association of lung Present address of the authors: Department of Pediatrics, Okayama University Medical School, Okayama (Director: Prof. E. Hamamoto) and * Department of Surgery, Okayama University Medical School, Okayama (Director: Pro£. T. Sunada)