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Significance of Newborn Age and Dose of Urethan in Leukemogenesis¹

Division of Oncology, Institute for Medical Research, Chicago Medical School, Chicago, Illinois

Urethan alone has been known to be slightly leukemogenic for newborn mice and even less so for the adults. The studies were made to determine whether infant mice have the same susceptibility to leukemogenesis as newborns in relationship to the dose of urethan delivered.

Urethan was injected repeatedly at 3 dose levels into C57BL x C3H F₁ mice starting when less than 24 hr old or at 7 days of age. The injections were given i.p. at 3-day intervals for a total of 6 times. The total dose of urethan delivered/gm body weight was 2.1, 3.0, or 4.2 mg.

The mice treated for the 1st time at newborn age developed leukemia of 7, 32, and 74% for 3 dose levels, respectively. However, the animals initially exposed to urethan when 7 days old showed a significantly lower incidence of 0, 7, and 38%. The positive linear dose-response relationship was found for both age groups between the total dose of urethan delivered and the incidence of leukemia.

The results demonstrated that 7-day-old mice are less susceptible than newborns to urethan leukemogenesis, which could be compensated for by increasing the dose of urethan. Findings also convincingly confirmed the leukemogenicity of urethan for mice. These observations were correlated with previous findings and discussed in relation to current knowledge concerning the high susceptibility of newborn mice to urethan leukemogenesis.

¹ This investigation was supported by Contract PH 43-65-67 from the National Cancer Institute, NIH, USPHS.

Received 12/21/65.