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Significance of Thymus and Marrow Injury in Urethan Leukemogenesis^*

Nechama Haran-Ghera and Henry S. Kaplan

( Department of Radiology, Stanford University School of Medicine, Palo Alto, California)

Urethan at a dose level of 1 mg/gm body weight caused histologic damage and reduction of thymus weight in mice of strain C57BL. Thymic injury was only slightly less severe in 30- to 60-day-old mice than in 1- to 20-day-old mice. Urethan also produced bone marrow injury in mice of this strain, expressed as a loss of the capacity to promote thymic regeneration in irradiated test mice, which was age-dependent, occurring in donors 30 days of age or less, but not in donors 2–3 months old. Urethan-treated marrow from young donors was also significantly less effective than normal marrow in inhibiting lymphoma development in irradiated isologous hosts. It is concluded that the age-dependent capacity of urethan to act as a complete leukemogen is paralleled and presumably explained by the age-limited character of the marrow injury which it produces. Urethan leukemogenesis thus closely resembles radiation leukemogenesis in mice of strain C57BL with respect to the important role of concomitant injury to two tissues, the thymus and the bone marrow.

^* This investigation was supported in part by research grant CA-03352 from the National Cancer Institute, National Institutes of Health, United States Public Health Service.

Eleanor Roosevelt Foundation Fellow, 1963–1964, on leave from The Weizmann Institute of Science, Rehovoth, Israel.

Received 5/25/64.