The concentrations of some apparent free amino acids in the liver of normal and tumorous rats differing in age, sex, or strain have been determined, and the effects of three methionine analogs (ethionine, a-methylmethionine, and N-methylmethionine) on these amino acids have been compared.
There was a marked effect of age on the apparent free lysine in the liver of normal, but not tumorous, male rats. The effect of ethionine on some apparent free amino acids in both male and female rats was modified by the age of the animals.
The concentration of apparent free arginine in the liver of normal male rats was lower than that in females, and there was a striking difference in the effect of ethionine on the apparent free methionine in the livers of the two sexes.
The concentration of apparent free glycine and threonine in the liver of normal Long-Evans rats was higher than that in normal Wistar rats.
The analogs, a-methylmethionine and N-methylmethionine, were ineffective as tumor growth-inhibitors. They were nontoxic to the animals and had a greater (a-methylmethionine) or lesser (N-methylmethionine) effect than ethionine on the apparent free methionine in the liver of female rats. A marked difference between ethionine and the other analogs in the effect on the amino acids studied in female rats was the higher concentration of apparent free glycine in the liver following ethionine injection.
Paper No. 122. This work was aided by grants from the American Cancer Society, U.S. Public Health Service, and the University of California. The authors are indebted to Mrs. Aiko Schick for technical assistance and to Theodore Nunes and Merle C. Shaw for the synthesis of the analogs.