The effect of diets containing an abundance of milk, liver, riboflavin, and xanthine on methylcholanthrene carcinogenesis.

The numerous attempts to influence the development and growth of neoplasms by means of vitamins and other nutritional elements have been comprehensively summarized by other investigators (8, 9, 20). The experiment described here was stimulated by the observation that the dialyzed grouffd livers of cancerresistant mice (JK), exhibit a higher level of xanthine dehydrogenase activity than do the dialyzed liver preparations of mice of a cancer-susceptible (C3H) strain (11). The mice of the JK strain were found also to be more tolerant to salicylaldehyde than were those of the C3H strain (21, 22). Xanthine dehydrogenase is a flavoprotein (2, 13), capable of oxidizing aldehydes as well as xanthines and found in high concentrations in milk and liver (2, 10, 12, 13, 19). Axelrod and Elvehjem (1) showed that the xanthine dehydrogenase activity of rat liver is greatly reduced in riboflavin deficiency and that this decrease parallels the degree of the deficiency. The effect of feeding excessive amounts of the precursors of xanthine dehydrogenase on enzyme activity of the liver has not been determined. This paper will be limited to a presentation and discussion of the results of feeding relatively enormous amounts of the dietary precursors of xanthine dehydrogenase to mice of the C3H strain. These mice have a relatively high susceptibility to spontaneous mammary carcinoma and methylcholanthrene tumors (7); and their livers, as compared with those of the resistant JK mice, exhibit a lower xanthine dehydrogenase activity (11). Xanthine, which is one of the normal substrates for xanthine dehydrogenase, was also included in this investigation because excessive amounts of either the substrate or uric acid, its oxidation product, inhibit the activity of xanthine dehydrogenase (10). It was thought that the inclusion of this substance in the diet might reduce the xanthine dehydro-