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Tumor Incidence and Cellularity in Lungs of Mice Given Various Dose Schedules of Urethan¹

Donner Laboratory and Lawrence Radiation Laboratory, University of California, Berkeley, California 94720

In a previous investigation of the effects of single versus fractionated doses of urethan, we found decreases in tumor yield on fractionation regardless of the size or spacing of the fractions. Other investigators, however, reported increases in tumor yield with certain fractionation schedules. It was thought possible that this difference in result was due to age differences in the mice. Repetition of the experiment with a range of ages, as reported here, still showed a decrease in tumor yield as a result of fractionation. An age effect was seen in that older animals had fewer tumors than younger ones when individual doses of 0.5 mg urethan/g body weight (mg/g) were given. This age effect was not apparent when the individual dose was 1.0 mg/g.

Other investigators have reported urethan-induced hyperplasia in the alveolar walls of lung tissue. Since such hyperplasia might indicate the presence of cells in an early stage of tumor development, a study intended to find whether there was a correlation between hyperplasia and tumor yield was undertaken. There was, however, no observable hyperplasia of alveolar cells in the lung. Cellularity per unit volume of lung did change with age. The number of cells correlated inversely with the alveolar space in fresh lung.

Some hypotheses are suggested to explain the differences between results obtained by other investigators and those obtained by us.

¹ This investigation was supported in part by Research Grant GM-10525 from the NIH, USPHS, to the Statistical Laboratory, University of California, Berkeley, and in part by the U. S. Atomic Energy Commission.

Received 7/15/69. Accepted 10/ 9/69.