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Development of Broad Spectrum of Tumors by Ethylnitrosourea in Mice and the Modifying Role of Age, Sex, and Strain¹

Department of Radiology [S. D. V., K. V. N. R., N. M.], and Department of Pathology [S. D. V., L. S. L.], The Pritzker School of Medicine, and Franklin McLean Memorial Research Institute [S. D. V.], University of Chicago,² Chicago, Illinois 60637, and Experimental Pathology Branch, National Cancer Institute, Bethesda, Maryland 20014 [J. M. R.]

The modifying role of age, sex, and strain upon the incidence, multiplicity, and spectrum of tumors induced by ethylnitrosourea, a short-acting carcinogen, has been studied. The first-generation (F₁) hybrids of C57BL/6J x C3HeB/FeJ and C3HeB/FeJ x A/J mice of both sexes were given single i.p. injections (60 or 120 µg/g) of ethylnitrosourea at 1, 15, or 42 days of age. Experimental animals were left to live their life-span, while the control groups were killed at 52, 90, 142, and 170 weeks of age, respectively.

Animals treated with ethylnitrosourea died, in general, by the 90th week of age due to development of tumors mainly in lung, liver, Harderian glands, stomach, ovaries, lymphoreticular system, kidneys, mammary gland, uterus, and nervous system. In contrast, few of the controls died during that same observational period.

The age of mice at the time of exposure to the carcinogen was one of the most important modifiers of tumor development in lung, liver, Harderian glands, stomach, kidneys, lymphoreticular system, nervous system, ovaries, and mammary glands. The sex of the animals influenced the development of liver tumors, Harderian gland tumors, and malignant lymphomas. The C3HeB/FeJ x A/J F₁ hybrids more readily developed lung tumors, while the C57BL/6 x C3HeB/FeJ F₁ mice were more susceptible to liver, Harderian gland, lymphoreticular system, ovarian, and mammary gland carcinogenesis.

¹ These investigations have been supported in part by Contract NIH-NCI-E-69-2087 from the National Cancer Institute; Grant 69-6 from the American Cancer Society, Illinois Division, Inc.; American Cancer Society Institutional Grant ACS-IN-41-I; General Research Support Grant USPHS-5-501; and USPHS Grant 5-PO6-RR-00409.

² Operated by the University of Chicago for the United States Atomic Energy Commission.

Received 11/ 5/73. Accepted 6/12/74.

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