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Additive Leukemogenicity of Urethan and X-irradiation in Infant and Young Adult Mice¹

Departments of Radiology [S. D. V., N. M., K. V. N. R.], Medicine [E. L. S.], and Pathology [L. S. L.], The Pritzker School of Medicine and the Argonne Cancer Research Hospital, The University of Chicago,² Chicago, Illinois 60637

The lymphoid system of adult mice does not respond readily to urethan treatment, so that administration of this agent before X-irradiation does not lead to an enhancement of radiation leukemogenesis. Presently, a two-stage experimental design has been used to evaluate mutual influence of these two exogenous carcinogenic agents on leukemogenesis when they are administered during responsive age periods.

The C57BL x C3H F₁ infant mice were exposed to subliminal amounts of urethan (ethyl carbamate) on the 3rd, 6th, and 12th days of life; this was followed by single or fractionated exposures to X-irradiation, first delivered at the 42nd day of age. The experiment was terminated after 56 weeks.

The results demonstrated that, due to existing susceptibility of infant mice to leukemogenesis by urethan, pretreatment with subliminal amounts of this agent during that age period strikingly augmented X-irradiation leukemogenesis. It has been concluded that biologically this enhancement represents a summation of individual leukemogenic effects.

¹ This investigation has been supported in part by 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-00409-04 from the A. J. Carlson Animal Research Facility.

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

Received 5/27/71. Accepted 10/ 7/71.