Studies on xanthine oxidase during carcinogenesis by p-dimethylaminoazobenzene.

Protein and riboflavin deficiencies (11, 17, 1, 7) seem to be major dietary factors involved in the production of liver cancers by feeding p-dimethylaminoazobenzene. The quantity and type of fat in the diet also appear to be important in this process (14, 18), and other dietary factors, such as biotin, play a role under certain conditions (8, 22). Con versely, a major effect of feeding p-dimethylaminoazobenzene is the depletion of liver riboflavin (6, 10, 16). This effect may well be related to its carcinogenic action, since p-dimethylaminoazobenzene does not have a similar effect on other tis sues, and noncarcinogenic dyes have little, if any, effect on the hepatic riboflavin. In order for p-dimethylaminoazobenzene to be a potent carcinogen, it must act Synergistically with a nutritional deficiency. Two important nutri tional factors related to this process, protein and riboflavin deficiencies, are the same dietary factors that are capable of depleting liver xanthine oxidase (24, 19, 2). Xanthine oxidase is a complex flavoprotein enzyme (3, 5) and is the only oxidative enzyme involved in the formation of uric acid from nucleotides; it is the only one of the enzymes in volved in nucleotide metabolism in rat liver that is appreciably affected by a low protein diet (20). Since these known interrelationships hold many implications of possible importance in the mecha nism of p-dimethylaminoazobenzene carcinogenesis, a study of the relationship of xanthine oxidase to the production of cancer by p-dimethylaminoazobenzene was undertaken.