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Biochemical Changes during Experimental Carcinogenesis

I. Amino Acid Metabolism in Perfused Livers of Rats with Cirrhosis and Azo Dye-fed Rats

William T. Burke and Leon L. Miller

( Department of Radiation Biology, School of Medicine and Dentistry, University of Rochester, Rochester, N.Y.)

The technic of perfusing isolated rat livers has been used to study amino acid metabolism in livers from rats which have been maintained on a 3'-Me-DAB diet and on a low protein-low choline diet producing experimental cirrhosis. The precancerous rat liver shows a marked depression of urea synthesis and a decreased production of C¹⁴O₂ from L-lysine-6-C¹⁴ during the course of 6-hr. experiments. At the end of the experiment these livers have significantly elevated liver free amino acid concentration. These findings are paralleled in the cirrhotic rat liver.

In the precancerous livers incorporation of L-lysine-6-C¹⁴ into both liver and plasma proteins is 2–3 times greater than into the liver and plasma proteins of normal livers. Similarly, the cirrhotic livers show increased incorporation into liver proteins and unimpaired incorporation into plasma proteins.

The data are indicative of an underlying biochemical defect in the amino acid catabolism of the precancerous and cirrhotic rat livers. This defect seems to involve the metabolism of -amino nitrogen and may reflect an impairment in the transamination or deamination systems of these livers or an impairment in one of the subsequent reactions leading to the synthesis of urea.

^* These studies were performed under contract with the the United States Atomic Energy Commission at the University of Rochester Atomic Energy Project, Rochester, New York, and were supported in part by a research grant from the Jane Coffin Childs Memorial Fund for Medical Research.

A preliminary report of these investigations was presented at the 39th Annual Meeting of the Federation of American Societies for Experimental Biology in San Francisco, April, 1955.

Postdoctoral fellow of the National Cancer Institute, United States Public Health Service.