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Comparative Studies on the Kinetics of the Neoplastic Competence in Mice¹

Department of Radiology, Pritzker School of Medicine, The University of Chicago, Chicago, Illinois 60637

In the current study, a comparison was made between tumor spectra resulting from the administration of urethan at different age periods and the tumors which developed late in life in the nontreated mice. C57BL x C3H F₁ hybrids were given urethan at 3-day intervals. The first injections were given on the 1st, 4th, or 175th day of life. The adult animals received either the same or a multiple of the amount of urethan given to 4-day-old mice. The urethan-treated groups were observed for 1 year, and the controls were observed for 154 weeks.

The nontreated controls developed leukemias, hepatomas, lung adenomas, Harderian gland adenomas, and ovarian tumors during their 3rd year of life. Neonatal exposure to urethan had a positive effect on the development of the same tumor types. The administration of the carcinogen to the adult animals resulted in the development of lung adenomas, Harderian gland adenomas, and ovarian tumors. The incidence of each of these primary tumors was directly related to the dose of the carcinogen administered. No leukemia developed in the adult animals in spite of the increased dose, while hepatomas were observed in a low incidence only in a group of mice exposed to the highest dose of urethan.

It was concluded that the tumor response to the carcinogen, both the spectrum and the incidence, was dependent upon the age of the animals at the time of the exposure to urethan regardless of the tendency of the tissues to develop tumors spontaneously.

¹ This investigation was supported in part by Grant 69-6 from the American Cancer Society, Illinois Division Inc., American Cancer Society Institutional Grant ACS-IN-41-I, and General Research Support Grant USPHS-5-501.

Received 4/ 9/70. Accepted 7/ 1/70.