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Studies on Xanthine Oxidase during Carcinogenesis by p-Dimethylaminoazobenzene^*

(From the Departments of Biochemistry and Pathology, Syracuse University College of Medicine, Syracuse, N.Y.)

Rats were fed purified diets containing 21 per cent, 12 per cent, or 8 per cent casein with or without added p-dimethylaminoazobenzene. At the end of 1, 2, and 4 months, six rats from each of the six dietary groups were analyzed for xanthine oxidase in the liver, kidney, lung, spleen, intestine, and blood. A method for determining blood xanthine oxidase was described.

By comparison with chow-fed rats, the purified 21 per cent casein diet alone decreased the xanthine oxidase somewhat in the liver, spleen, lung, and intestine, but not in the kidney. The 8 per cent casein diet gave a further marked decrease in the liver enzyme only, and a marked increase in the blood xanthine oxidase.

p-Dimethylaminoazobenzene decreased the xanthine oxidase in kidney and blood, irrespective of diet, and decreased the enzyme in liver synergistically with a low protein intake; the dye had no depressant effect on the xanthine oxidase in lung, spleen, or intestine.

The same xanthine oxidase activity was found in the liver homogenates after dialysis. The activity of added milk xanthine oxidase was increased slightly more in the liver homogenates of dye-free rats than in dye-fed rats. Methylene blue added to the liver homogenate in the aerobic test system increased the xanthine oxidase activity more in the dye-fed rats than in the controls. The effect of methylene blue on the xanthine oxidase activity of the liver homogenate was lost on dialysis, especially with livers from the low protein groups. These results indicated that the livers of dye-fed rats contained a small amount of nondialyzable inhibitor of xanthine oxidase that affected primarily the auto-oxidizable rather than the dehydrogenase portion of the enzyme. The livers also contained less enzyme than the dye-free controls. The effect of the dye in decreasing the endogenous respiration of the liver homogenate was due to a decreased xanthine oxidase activity of the liver.

The low protein diets were characterized by fatty infiltration and hydropic degeneration of the liver. Dye feeding led to bile-duct proliferation and cystadenomas in the 21 per cent casein group and bile-duct carcinomas in the other dietary groups.

^* This work was done under a grant-in-aid from the American Cancer Society upon recommendation of the Committee on Growth of the National Research Council.

Received 4/ 3/50.